11-77157326-T-C

Variant names:

• chr11-77157326-T-C
• rs762667
• NM_000260.4:c.783T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000260.4(MYO7A):​c.783T>C​(p.Gly261Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,610,282 control chromosomes in the GnomAD database, including 123,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G261G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.49 (20589 hom., cov: 34)
  • Exomes 𝑓: 0.37 (103075 hom.)
• Consequence: MYO7A NM_000260.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: -0.0660
• Publications: 23 publications found

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]

MYO7A Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Usher syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Usher syndrome type 1B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss 11

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Usher syndrome type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 11-77157326-T-C is Benign according to our data. Variant chr11-77157326-T-C is described in ClinVar as Benign. ClinVar VariationId is 43343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.066 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	NM_000260.4	MANE Select	c.783T>C	p.Gly261Gly	synonymous	Exon 8 of 49	NP_000251.3	Q13402-1
	MYO7A	NM_001127180.2		c.783T>C	p.Gly261Gly	synonymous	Exon 8 of 49	NP_001120652.1	Q13402-2
	MYO7A	NM_001369365.1		c.750T>C	p.Gly250Gly	synonymous	Exon 9 of 50	NP_001356294.1	Q13402-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.783T>C	p.Gly261Gly	synonymous	Exon 8 of 49	ENSP00000386331.3	Q13402-1
	MYO7A	ENST00000458637.6	TSL:1	c.783T>C	p.Gly261Gly	synonymous	Exon 8 of 49	ENSP00000392185.2	Q13402-2
	MYO7A	ENST00000409619.6	TSL:1	c.750T>C	p.Gly250Gly	synonymous	Exon 9 of 50	ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73932 AN: 151848 Hom.: 20543 Cov.: 34

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.443

GnomAD2 exomes AF: 0.388 AC: 94800 AN: 244088 AF XY: 0.370

Gnomad AFR exome AF: 0.775

Gnomad AMR exome AF: 0.470

Gnomad ASJ exome AF: 0.326

Gnomad EAS exome AF: 0.324

Gnomad FIN exome AF: 0.455

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.364

GnomAD4 exome AF: 0.367 AC: 535874 AN: 1458316 Hom.: 103075 Cov.: 40 AF XY: 0.362 AC XY: 262121 AN XY: 725086

African (AFR) AF: 0.784 AC: 26197 AN: 33432

American (AMR) AF: 0.467 AC: 20646 AN: 44198

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 8465 AN: 26086

East Asian (EAS) AF: 0.324 AC: 12846 AN: 39612

South Asian (SAS) AF: 0.224 AC: 19175 AN: 85648

European-Finnish (FIN) AF: 0.460 AC: 24478 AN: 53194

Middle Eastern (MID) AF: 0.346 AC: 1997 AN: 5764

European-Non Finnish (NFE) AF: 0.360 AC: 399842 AN: 1110098

Other (OTH) AF: 0.369 AC: 22228 AN: 60284

GnomAD4 genome AF: 0.487 AC: 74031 AN: 151966 Hom.: 20589 Cov.: 34 AF XY: 0.486 AC XY: 36136 AN XY: 74280

African (AFR) AF: 0.766 AC: 31780 AN: 41476

American (AMR) AF: 0.457 AC: 6977 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3472

East Asian (EAS) AF: 0.327 AC: 1683 AN: 5142

South Asian (SAS) AF: 0.222 AC: 1063 AN: 4796

European-Finnish (FIN) AF: 0.470 AC: 4960 AN: 10562

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25042 AN: 67920

Other (OTH) AF: 0.440 AC: 929 AN: 2112

Alfa AF: 0.380 Hom.: 20148

Bravo AF: 0.498

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Autosomal dominant nonsyndromic hearing loss 11 (2)
-	-	2	Autosomal recessive nonsyndromic hearing loss 2 (2)
-	-	2	Usher syndrome type 1 (2)
-	-	1	Usher syndrome type 1;C1832475:Autosomal dominant nonsyndromic hearing loss 11;C1838701:Autosomal recessive nonsyndromic hearing loss 2 (1)
-	-	1	Usher syndrome type 1B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.4
DANN	Benign	0.74
PhyloP100		-0.066
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs762667; hg19: chr11-76868372; COSMIC: COSV68683778;