11-77142783-C-T

Variant names:

• chr11-77142783-C-T
• rs35689081
• NM_000260.4:c.93C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000260.4(MYO7A):​c.93C>T​(p.Cys31Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,610,834 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (51 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (45 hom.)
• Consequence: MYO7A NM_000260.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.730
• Publications: 13 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 11-77142783-C-T is Benign according to our data. Variant chr11-77142783-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0518 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.93C>T	p.Cys31Cys	synonymous	Exon 3 of 49	NP_000251.3	Q13402-1
	MYO7A	NM_001127180.2		c.93C>T	p.Cys31Cys	synonymous	Exon 3 of 49	NP_001120652.1	Q13402-2
	MYO7A	NM_001369365.1		c.60C>T	p.Cys20Cys	synonymous	Exon 4 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.93C>T	p.Cys31Cys	synonymous	Exon 3 of 49	ENSP00000386331.3	Q13402-1
	MYO7A	ENST00000458637.6	TSL:1	c.93C>T	p.Cys31Cys	synonymous	Exon 3 of 49	ENSP00000392185.2	Q13402-2
	MYO7A	ENST00000409619.6	TSL:1	c.60C>T	p.Cys20Cys	synonymous	Exon 4 of 50	ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2319 AN: 152136 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00358 AC: 866 AN: 242144 AF XY: 0.00247

Gnomad AFR exome AF: 0.0533

Gnomad AMR exome AF: 0.00195

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000546

Gnomad OTH exome AF: 0.00118

GnomAD4 exome AF: 0.00143 AC: 2093 AN: 1458580 Hom.: 45 Cov.: 33 AF XY: 0.00118 AC XY: 858 AN XY: 725086

African (AFR) AF: 0.0523 AC: 1751 AN: 33452

American (AMR) AF: 0.00203 AC: 90 AN: 44334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39594

South Asian (SAS) AF: 0.000129 AC: 11 AN: 85062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1110786

Other (OTH) AF: 0.00319 AC: 192 AN: 60280

GnomAD4 genome AF: 0.0153 AC: 2325 AN: 152254 Hom.: 51 Cov.: 33 AF XY: 0.0141 AC XY: 1046 AN XY: 74438

African (AFR) AF: 0.0537 AC: 2230 AN: 41530

American (AMR) AF: 0.00438 AC: 67 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68020

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00115 Hom.: 23

Bravo AF: 0.0167

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	6.4
DANN	Benign	0.68
PhyloP100		-0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

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: rs35689081; hg19: chr11-76853829;