chr11-77198503-C-G

Position:

• chr11-77198503-C-G

Variant summary

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

The NM_000260.4(MYO7A):​c.4450C>G​(p.Leu1484Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYO7A NM_000260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.45

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 (HGNC:):

ACMG classification

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	c.4450C>G	p.Leu1484Val	missense_variant	34/49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.4450C>G	p.Leu1484Val	missense_variant	34/49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.4450C>G	p.Leu1484Val	missense_variant	34/49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.4417C>G	p.Leu1473Val	missense_variant	35/50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.1993C>G	p.Leu665Val	missense_variant	14/29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.2290C>G		non_coding_transcript_exon_variant	17/32			ENSP00000499323.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248864 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135088

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Pathogenic	0.24
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D;.;.;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Pathogenic	0.84	D
MutationAssessor	Uncertain	2.3	M;M;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Uncertain	0.64
Sift	Benign	0.043	D;D;D;D
Sift4G	Uncertain	0.059	T;T;T;T
Polyphen		0.043	B;.;.;.
Vest4		0.79
MutPred		0.37		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;.;
MVP		0.93
MPC		0.16
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.43
gMVP		0.44

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: rs200416912; hg19: chr11-76909548;