Variant 11-77190870-G-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.3924G>T(p.Lys1308Asn) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K1308K) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MYO7A
NM_000260.4 missense, splice_region

Scores

Splicing: ADA: 1.000

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.40

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:

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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 link	c.3924G>T	p.Lys1308Asn	missense_variant, splice_region_variant	30/49	ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 link	c.3924G>T	p.Lys1308Asn	missense_variant, splice_region_variant	30/49	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.3924G>T	p.Lys1308Asn	missense_variant, splice_region_variant	30/49	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.3891G>T	p.Lys1297Asn	missense_variant, splice_region_variant	31/50	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 link	c.1467G>T	p.Lys489Asn	missense_variant, splice_region_variant	10/29	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 link	n.1764G>T		splice_region_variant, non_coding_transcript_exon_variant	13/32			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1403324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690198

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.091

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.77

D;.;.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.72

D;D;D;D

MetaSVM

Uncertain

0.39

MutationAssessor

Pathogenic

3.1

M;M;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-4.6

D;D;D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Benign

0.067

T;T;T;D

Polyphen

0.81

P;.;.;.

Vest4

0.87

MutPred

0.41

Loss of ubiquitination at K1308 (P = 0.0174);Loss of ubiquitination at K1308 (P = 0.0174);.;.;

MVP

0.93

MPC

0.29

ClinPred

0.99

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.78

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.98

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.30

Position offset: -37

DS_DL_spliceai

0.39

Position offset: 0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over