rs56174006

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_000260.4(MYO7A):​c.4461C>T​(p.Asn1487Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0052 in 1,613,848 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0059 ( 8 hom., cov: 33)
Exomes 𝑓: 0.0051 ( 28 hom. )

Consequence

MYO7A
NM_000260.4 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:10

Conservation

PhyloP100: -1.98
Variant links:
Genes affected
MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 11-77198514-C-T is Benign according to our data. Variant chr11-77198514-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43242.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=2, Benign=5}. Variant chr11-77198514-C-T is described in Lovd as [Benign]. Variant chr11-77198514-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.98 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00587 (894/152314) while in subpopulation AFR AF= 0.00864 (359/41562). AF 95% confidence interval is 0.0079. There are 8 homozygotes in gnomad4. There are 404 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYO7ANM_000260.4 linkc.4461C>T p.Asn1487Asn synonymous_variant 34/49 ENST00000409709.9 NP_000251.3 Q13402-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYO7AENST00000409709.9 linkc.4461C>T p.Asn1487Asn synonymous_variant 34/491 NM_000260.4 ENSP00000386331.3 Q13402-1
MYO7AENST00000458637.6 linkc.4461C>T p.Asn1487Asn synonymous_variant 34/491 ENSP00000392185.2 Q13402-2
MYO7AENST00000409619.6 linkc.4428C>T p.Asn1476Asn synonymous_variant 35/501 ENSP00000386635.2 Q13402-8
MYO7AENST00000458169.2 linkc.2004C>T p.Asn668Asn synonymous_variant 14/291 ENSP00000417017.2 H7C4D8
MYO7AENST00000670577.1 linkn.2301C>T non_coding_transcript_exon_variant 17/32 ENSP00000499323.1 A0A590UJ94

Frequencies

GnomAD3 genomes
AF:
0.00587
AC:
894
AN:
152196
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00866
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00510
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00123
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00604
Gnomad OTH
AF:
0.00764
GnomAD3 exomes
AF:
0.00394
AC:
980
AN:
248926
Hom.:
3
AF XY:
0.00403
AC XY:
545
AN XY:
135114
show subpopulations
Gnomad AFR exome
AF:
0.00990
Gnomad AMR exome
AF:
0.00261
Gnomad ASJ exome
AF:
0.00179
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.00193
Gnomad FIN exome
AF:
0.00135
Gnomad NFE exome
AF:
0.00544
Gnomad OTH exome
AF:
0.00265
GnomAD4 exome
AF:
0.00513
AC:
7501
AN:
1461534
Hom.:
28
Cov.:
31
AF XY:
0.00507
AC XY:
3688
AN XY:
727056
show subpopulations
Gnomad4 AFR exome
AF:
0.0103
Gnomad4 AMR exome
AF:
0.00239
Gnomad4 ASJ exome
AF:
0.00153
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00203
Gnomad4 FIN exome
AF:
0.00156
Gnomad4 NFE exome
AF:
0.00578
Gnomad4 OTH exome
AF:
0.00472
GnomAD4 genome
AF:
0.00587
AC:
894
AN:
152314
Hom.:
8
Cov.:
33
AF XY:
0.00542
AC XY:
404
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00864
Gnomad4 AMR
AF:
0.00510
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00186
Gnomad4 FIN
AF:
0.00123
Gnomad4 NFE
AF:
0.00604
Gnomad4 OTH
AF:
0.00756
Alfa
AF:
0.00519
Hom.:
1
Bravo
AF:
0.00624

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:10
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Benign:4
Benign, criteria provided, single submitterclinical testingGeneDxSep 06, 2012This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Oct 16, 2014- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 25, 2011Asn1487Asn in exon 34 of MYO7A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located in a splice site and has been identified in 2% of cases. -
not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2024MYO7A: BP4, BP7, BS2 -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Usher syndrome type 1 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabMay 18, 2021- -
Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Autosomal dominant nonsyndromic hearing loss 11 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Usher syndrome type 1B Benign:1
Benign, no assertion criteria providedclinical testingNatera, Inc.Sep 16, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.32
DANN
Benign
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56174006; hg19: chr11-76909559; API