11-77199721-C-T

Variant names:

• chr11-77199721-C-T
• rs7927472
• NM_000260.4:c.4755C>T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000260.4(MYO7A):​c.4755C>T​(p.Ser1585Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,612,982 control chromosomes in the GnomAD database, including 222,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17986 hom., cov: 32)
  • Exomes 𝑓: 0.52 (204172 hom.)
• Consequence: MYO7A NM_000260.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 2.84

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 11-77199721-C-T is Benign according to our data. Variant chr11-77199721-C-T is described in ClinVar as [Benign]. Clinvar id is 43257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77199721-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.4755C>T	p.Ser1585Ser	synonymous_variant	Exon 35 of 49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.4755C>T	p.Ser1585Ser	synonymous_variant	Exon 35 of 49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.4641C>T	p.Ser1547Ser	synonymous_variant	Exon 35 of 49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.4608C>T	p.Ser1536Ser	synonymous_variant	Exon 36 of 50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.2184C>T	p.Ser728Ser	synonymous_variant	Exon 15 of 29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.2595C>T		non_coding_transcript_exon_variant	Exon 18 of 32			ENSP00000499323.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72128 AN: 151978 Hom.: 17976 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.492

GnomAD3 exomes AF: 0.514 AC: 127220 AN: 247600 Hom.: 33920 AF XY: 0.505 AC XY: 67902 AN XY: 134372

Gnomad AFR exome AF: 0.325

Gnomad AMR exome AF: 0.641

Gnomad ASJ exome AF: 0.405

Gnomad EAS exome AF: 0.485

Gnomad SAS exome AF: 0.358

Gnomad FIN exome AF: 0.621

Gnomad NFE exome AF: 0.538

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.524 AC: 765649 AN: 1460886 Hom.: 204172 Cov.: 51 AF XY: 0.519 AC XY: 377181 AN XY: 726700

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.633

Gnomad4 ASJ exome AF: 0.396

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.620

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.474 AC: 72159 AN: 152096 Hom.: 17986 Cov.: 32 AF XY: 0.479 AC XY: 35589 AN XY: 74348

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.491

Alfa AF: 0.499 Hom.: 11106

Bravo AF: 0.470

Asia WGS AF: 0.402 AC: 1398 AN: 3478

EpiCase AF: 0.527

EpiControl AF: 0.527

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Mar 08, 2007

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 11, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 11 Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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. -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 2 Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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. -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1 Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	11
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs7927472; hg19: chr11-76910766; COSMIC: COSV68687506; COSMIC: COSV68687506;