rs797044513

Variant names:

• chr11-77189404-TGCCCGGG-A
• rs797044513
• NM_000260.4:c.3564_3571delTGCCCGGGinsA

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000260.4(MYO7A):​c.3564_3571delTGCCCGGGinsA​(p.Tyr1188fs) variant causes a frameshift, stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYO7A NM_000260.4 frameshift, stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 9.59

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 Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-77189404-TGCCCGGG-A is Pathogenic according to our data. Variant chr11-77189404-TGCCCGGG-A is described in ClinVar as [Pathogenic]. Clinvar id is 179061.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.3564_3571delTGCCCGGGinsA	p.Tyr1188fs	frameshift_variant, stop_gained	Exon 28 of 49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.3564_3571delTGCCCGGGinsA	p.Tyr1188fs	frameshift_variant, stop_gained	Exon 28 of 49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.3564_3571delTGCCCGGGinsA	p.Tyr1188fs	frameshift_variant, stop_gained	Exon 28 of 49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.3531_3538delTGCCCGGGinsA	p.Tyr1177fs	frameshift_variant, stop_gained	Exon 29 of 50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.1107_1114delTGCCCGGGinsA	p.Tyr369fs	frameshift_variant, stop_gained	Exon 8 of 29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.1404_1411delTGCCCGGGinsA		non_coding_transcript_exon_variant	Exon 11 of 32			ENSP00000499323.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Rare genetic deafness Pathogenic:1

May 13, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The Tyr1188X variant in MYO7A has not been reported in individuals with hearing loss or in large population databases. This variant is predicted to result in a premature termination codon at position 1188, which would lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified a s pathogenic (http://pcpgm.partners.org/LMM). -

Retinal dystrophy Pathogenic:1

Jan 01, 2021

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs797044513; hg19: chr11-76900449;