11-77183418-C-T

Variant names:

• chr11-77183418-C-T
• rs3758708
• NM_000260.4:c.3375+261C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000409709.9(MYO7A):​c.3375+261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 152,174 control chromosomes in the GnomAD database, including 762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.095 (762 hom., cov: 32)
• Consequence: MYO7A ENST00000409709.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75
• Publications: 5 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, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
• Usher syndrome type 1

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

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

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-77183418-C-T is Benign according to our data. Variant chr11-77183418-C-T is described in ClinVar as Benign. ClinVar VariationId is 1288435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409709.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	NM_000260.4	MANE Select	c.3375+261C>T		intron	N/A	NP_000251.3
	MYO7A	NM_001127180.2		c.3375+261C>T		intron	N/A	NP_001120652.1
	MYO7A	NM_001369365.1		c.3342+261C>T		intron	N/A	NP_001356294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.3375+261C>T		intron	N/A	ENSP00000386331.3
	MYO7A	ENST00000458637.6	TSL:1	c.3375+261C>T		intron	N/A	ENSP00000392185.2
	MYO7A	ENST00000409619.6	TSL:1	c.3342+261C>T		intron	N/A	ENSP00000386635.2

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14384 AN: 152056 Hom.: 762 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0660

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0779

Gnomad OTH AF: 0.0920

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0946 AC: 14402 AN: 152174 Hom.: 762 Cov.: 32 AF XY: 0.0950 AC XY: 7070 AN XY: 74412

African (AFR) AF: 0.111 AC: 4610 AN: 41506

American (AMR) AF: 0.149 AC: 2284 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 205 AN: 3468

East Asian (EAS) AF: 0.134 AC: 692 AN: 5176

South Asian (SAS) AF: 0.0661 AC: 319 AN: 4826

European-Finnish (FIN) AF: 0.0500 AC: 530 AN: 10610

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0779 AC: 5299 AN: 67988

Other (OTH) AF: 0.0934 AC: 197 AN: 2110

Alfa AF: 0.0837 Hom.: 854

Bravo AF: 0.104

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.60
PhyloP100		-1.7
Mutation Taster		=100/0	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: rs3758708; hg19: chr11-76894463;