rs376764423

Variant names:

• chr11-77208472-C-A
• rs376764423
• NM_000260.4:c.5899C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-77208472-C-A
• chr11-77208472-C-G
• chr11-77208472-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000260.4(MYO7A):​c.5899C>A​(p.Arg1967Arg) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYO7A NM_000260.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.5899C>A	p.Arg1967Arg	synonymous_variant	Exon 43 of 49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.5899C>A	p.Arg1967Arg	synonymous_variant	Exon 43 of 49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.5785C>A	p.Arg1929Arg	synonymous_variant	Exon 43 of 49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.5752C>A	p.Arg1918Arg	synonymous_variant	Exon 44 of 50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.3325C>A	p.Arg1109Arg	synonymous_variant	Exon 23 of 29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.*497C>A		non_coding_transcript_exon_variant	Exon 26 of 32			ENSP00000499323.1
MYO7A	ENST00000670577	n.*497C>A		3_prime_UTR_variant	Exon 26 of 30			ENSP00000499323.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461392 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726966

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.86		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.86		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs376764423; hg19: chr11-76919517;