rs77568474

Positions:

• chr11-77161165-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000260.4(MYO7A):​c.1343+50T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000928 in 1,608,020 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00096 (1 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.663

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-77161165-T-A is Benign according to our data. Variant chr11-77161165-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 255660.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO7A	NM_000260.4	c.1343+50T>A		intron_variant		ENST00000409709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO7A	ENST00000409709.9	c.1343+50T>A		intron_variant		1	NM_000260.4
MYO7A	ENST00000409619.6	c.1310+50T>A		intron_variant		1
MYO7A	ENST00000458637.6	c.1343+50T>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.000658 AC: 100 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000788 AC: 195 AN: 247386 Hom.: 0 AF XY: 0.000865 AC XY: 116 AN XY: 134180

Gnomad AFR exome AF: 0.000390

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00171

Gnomad EAS exome AF: 0.000112

Gnomad SAS exome AF: 0.00185

Gnomad FIN exome AF: 0.000233

Gnomad NFE exome AF: 0.000919

Gnomad OTH exome AF: 0.000667

GnomAD4 exome AF: 0.000957 AC: 1393 AN: 1455814 Hom.: 1 Cov.: 30 AF XY: 0.000950 AC XY: 687 AN XY: 723510

Gnomad4 AFR exome AF: 0.0000900

Gnomad4 AMR exome AF: 0.0000674

Gnomad4 ASJ exome AF: 0.00162

Gnomad4 EAS exome AF: 0.000379

Gnomad4 SAS exome AF: 0.00146

Gnomad4 FIN exome AF: 0.000244

Gnomad4 NFE exome AF: 0.00103

Gnomad4 OTH exome AF: 0.000831

GnomAD4 genome AF: 0.000657 AC: 100 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.000672 AC XY: 50 AN XY: 74416

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.000971

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.000589

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.40

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: rs77568474; hg19: chr11-76872211;