rs111033180

Positions:

• chr11-77172850-C-A
• chr11-77172850-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The ENST00000409709.9(MYO7A):​c.1900C>A​(p.Arg634=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MYO7A ENST00000409709.9 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.50

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.14).
• BP6: Variant 11-77172850-C-A is Benign according to our data. Variant chr11-77172850-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1648674.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.1900C>A	p.Arg634=	synonymous_variant	16/49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.1900C>A	p.Arg634=	synonymous_variant	16/49	1	NM_000260.4	ENSP00000386331
MYO7A	ENST00000458637.6	c.1900C>A	p.Arg634=	synonymous_variant	16/49	1		ENSP00000392185	P1
MYO7A	ENST00000409619.6	c.1867C>A	p.Arg623=	synonymous_variant	17/50	1		ENSP00000386635
MYO7A	ENST00000669443.1	c.265C>A	p.Arg89=	synonymous_variant	3/3			ENSP00000499530

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399830 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 690480

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 03, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	13
DANN	Benign	0.72

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: rs111033180; hg19: chr11-76883896;