10-26021541-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_017433.5(MYO3A):​c.624C>T​(p.Asp208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 1,613,856 control chromosomes in the GnomAD database, including 6,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 514 hom., cov: 32)
Exomes 𝑓: 0.086 ( 5899 hom. )

Consequence

MYO3A
NM_017433.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.73
Variant links:
Genes affected
MYO3A (HGNC:7601): (myosin IIIA) The protein encoded by this gene belongs to the myosin superfamily. Myosins are actin-dependent motor proteins and are categorized into conventional myosins (class II) and unconventional myosins (classes I and III through XV) based on their variable C-terminal cargo-binding domains. Class III myosins, such as this one, have a kinase domain N-terminal to the conserved N-terminal motor domains and are expressed in photoreceptors. The protein encoded by this gene plays an important role in hearing in humans. Three different recessive, loss of function mutations in the encoded protein have been shown to cause nonsyndromic progressive hearing loss. Expression of this gene is highly restricted, with the strongest expression in retina and cochlea. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
Variant 10-26021541-C-T is Benign according to our data. Variant chr10-26021541-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 45820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-26021541-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=2.73 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYO3ANM_017433.5 linkuse as main transcriptc.624C>T p.Asp208= synonymous_variant 8/35 ENST00000642920.2 NP_059129.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYO3AENST00000642920.2 linkuse as main transcriptc.624C>T p.Asp208= synonymous_variant 8/35 NM_017433.5 ENSP00000495965 P1Q8NEV4-1

Frequencies

GnomAD3 genomes
AF:
0.0778
AC:
11837
AN:
152076
Hom.:
511
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0647
Gnomad AMI
AF:
0.0154
Gnomad AMR
AF:
0.0862
Gnomad ASJ
AF:
0.0978
Gnomad EAS
AF:
0.000962
Gnomad SAS
AF:
0.0290
Gnomad FIN
AF:
0.0692
Gnomad MID
AF:
0.0728
Gnomad NFE
AF:
0.0944
Gnomad OTH
AF:
0.0794
GnomAD3 exomes
AF:
0.0707
AC:
17779
AN:
251384
Hom.:
807
AF XY:
0.0709
AC XY:
9631
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.0671
Gnomad AMR exome
AF:
0.0557
Gnomad ASJ exome
AF:
0.0928
Gnomad EAS exome
AF:
0.000598
Gnomad SAS exome
AF:
0.0321
Gnomad FIN exome
AF:
0.0701
Gnomad NFE exome
AF:
0.0952
Gnomad OTH exome
AF:
0.0808
GnomAD4 exome
AF:
0.0859
AC:
125527
AN:
1461662
Hom.:
5899
Cov.:
35
AF XY:
0.0845
AC XY:
61451
AN XY:
727144
show subpopulations
Gnomad4 AFR exome
AF:
0.0664
Gnomad4 AMR exome
AF:
0.0588
Gnomad4 ASJ exome
AF:
0.0918
Gnomad4 EAS exome
AF:
0.000403
Gnomad4 SAS exome
AF:
0.0332
Gnomad4 FIN exome
AF:
0.0736
Gnomad4 NFE exome
AF:
0.0956
Gnomad4 OTH exome
AF:
0.0815
GnomAD4 genome
AF:
0.0778
AC:
11845
AN:
152194
Hom.:
514
Cov.:
32
AF XY:
0.0762
AC XY:
5668
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.0647
Gnomad4 AMR
AF:
0.0861
Gnomad4 ASJ
AF:
0.0978
Gnomad4 EAS
AF:
0.000964
Gnomad4 SAS
AF:
0.0288
Gnomad4 FIN
AF:
0.0692
Gnomad4 NFE
AF:
0.0944
Gnomad4 OTH
AF:
0.0795
Alfa
AF:
0.0893
Hom.:
321
Bravo
AF:
0.0793
Asia WGS
AF:
0.0340
AC:
120
AN:
3478
EpiCase
AF:
0.0930
EpiControl
AF:
0.103

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxAug 03, 2017This 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, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMay 07, 2012Asp208Asp in Exon 08 of MYO3A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 9.6% (677/7020) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs35010955). -
Autosomal recessive nonsyndromic hearing loss 30 Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.25
CADD
Benign
13
DANN
Benign
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs35010955; hg19: chr10-26310470; API