Variant 11-77203068-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000260.4(MYO7A):c.5177C>T(p.Pro1726Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000358 in 1,395,686 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

MYO7A
NM_000260.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:3

Conservation

PhyloP100: 5.71

Variant links:

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 links:

MYO7A (HGNC:):

MYO7A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4 linkuse as main transcript	c.5177C>T	p.Pro1726Leu	missense_variant	38/49	ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 linkuse as main transcript	c.5177C>T	p.Pro1726Leu	missense_variant	38/49	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 linkuse as main transcript	c.5063C>T	p.Pro1688Leu	missense_variant	38/49	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 linkuse as main transcript	c.5030C>T	p.Pro1677Leu	missense_variant	39/50	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 linkuse as main transcript	c.2603C>T	p.Pro868Leu	missense_variant	18/29	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 linkuse as main transcript	n.3017C>T		non_coding_transcript_exon_variant	21/32			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000134

AC:

AN:

149082

Hom.:

AF XY:

0.0000251

AC XY:

AN XY:

79676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000440

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000358

AC:

AN:

1395686

Hom.:

Cov.:

AF XY:

0.00000581

AC XY:

AN XY:

688440

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000506

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Pathogenic:1Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Dec 20, 2022	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23770805) -
Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Jan 15, 2019	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2021	- -

Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Counsyl

Dec 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.74

D;.;.;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Pathogenic

0.31

MetaRNN

Uncertain

0.51

D;D;D;D

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.9

M;.;.;.

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-6.6

D;D;D;D

REVEL

Benign

0.27

Sift

Benign

0.058

T;T;T;T

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.23

B;.;.;.

Vest4

0.59

MutPred

0.26

Loss of glycosylation at P1726 (P = 0.0142);.;.;.;

MVP

0.82

MPC

0.27

ClinPred

0.88

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.53

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over