rs397516327

Positions:

• chr11-77211265-C-A
• chr11-77211265-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000260.4(MYO7A):​c.6165C>A​(p.Ser2055Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S2055S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MYO7A NM_000260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33405364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO7A	NM_000260.4	c.6165C>A	p.Ser2055Arg	missense_variant	45/49	ENST00000409709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO7A	ENST00000409709.9	c.6165C>A	p.Ser2055Arg	missense_variant	45/49	1	NM_000260.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428586 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 707412

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.62	D;.;.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.7	L;.;.;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Benign	0.29
Sift	Benign	0.23	T;T;T;D
Sift4G	Benign	0.33	T;T;T;D
Polyphen		0.46	P;.;.;.
Vest4		0.61
MutPred		0.38		Loss of ubiquitination at K2058 (P = 0.0428);.;.;.;
MVP		0.82
MPC		0.12
ClinPred		0.98	D
GERP RS		-2.3
Varity_R		0.80
gMVP		0.40

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: rs397516327; hg19: chr11-76922310;