11-77192155-G-T

Variant names:

• chr11-77192155-G-T
• rs763469001
• NM_000260.4:c.4029G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000260.4(MYO7A):​c.4029G>T​(p.Arg1343Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYO7A NM_000260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.4029G>T	p.Arg1343Ser	missense_variant	Exon 31 of 49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.4029G>T	p.Arg1343Ser	missense_variant	Exon 31 of 49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.4029G>T	p.Arg1343Ser	missense_variant	Exon 31 of 49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.3996G>T	p.Arg1332Ser	missense_variant	Exon 32 of 50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.1572G>T	p.Arg524Ser	missense_variant	Exon 11 of 29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.1869G>T		non_coding_transcript_exon_variant	Exon 14 of 32			ENSP00000499323.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 249034 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135136

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461626 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727088

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.25
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	D;.;.;T
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.85	D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.6	M;M;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.7	D;D;D;D
REVEL	Pathogenic	0.71
Sift	Benign	0.043	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.91
MutPred		0.57		Loss of MoRF binding (P = 0.0254);Loss of MoRF binding (P = 0.0254);.;.;
MVP		0.87
MPC		0.49
ClinPred		1.0	D
GERP RS		0.33
Varity_R		0.77
gMVP		0.79

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: rs763469001; hg19: chr11-76903200;