11-77182575-T-C

Variant names:

• chr11-77182575-T-C
• rs375050157
• NM_000260.4:c.3260T>C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_000260.4(MYO7A):​c.3260T>C​(p.Leu1087Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: MYO7A NM_000260.4 missense
• Clinical Significance: no classification for the single variant no classification for the single variant U:1
• Conservation: PhyloP100: 7.63

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 5 ACMG points.

• PM1: In a domain MyTH4 1 (size 236) in uniprot entity MYO7A_HUMAN there are 26 pathogenic changes around while only 4 benign (87%) in NM_000260.4
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.3260T>C	p.Leu1087Pro	missense_variant	Exon 25 of 49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.3260T>C	p.Leu1087Pro	missense_variant	Exon 25 of 49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.3260T>C	p.Leu1087Pro	missense_variant	Exon 25 of 49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.3227T>C	p.Leu1076Pro	missense_variant	Exon 26 of 50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.803T>C	p.Leu268Pro	missense_variant	Exon 5 of 29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.1100T>C		non_coding_transcript_exon_variant	Exon 8 of 32			ENSP00000499323.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Significance: no classification for the single variant

Submissions summary: Uncertain:1

Revision: no classification for the single variant

Submissions by phenotype

Usher syndrome type 1 Uncertain:1

Jun 01, 2002

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	D;T;.;.;.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Pathogenic	0.46	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	2.0	M;.;M;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.5	D;.;D;D;.;D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.012	D;.;D;D;.;D
Sift4G	Benign	0.13	T;T;T;T;.;T
Polyphen		0.99	D;.;.;.;.;.
Vest4		0.94
MutPred		0.48		Gain of ubiquitination at K1084 (P = 0.0645);Gain of ubiquitination at K1084 (P = 0.0645);Gain of ubiquitination at K1084 (P = 0.0645);.;.;.;
MVP		0.93
MPC		0.59
ClinPred		0.96	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.88
gMVP		0.72

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: rs375050157; hg19: chr11-76893620;