11-77211192-G-C

Position:

• chr11-77211192-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000260.4(MYO7A):​c.6092G>C​(p.Arg2031Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,440,796 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MYO7A NM_000260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.57

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.6092G>C	p.Arg2031Pro	missense_variant	45/49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.6092G>C	p.Arg2031Pro	missense_variant	45/49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.5978G>C	p.Arg1993Pro	missense_variant	45/49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.5945G>C	p.Arg1982Pro	missense_variant	46/50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.3518G>C	p.Arg1173Pro	missense_variant	25/29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.*664G>C		non_coding_transcript_exon_variant	28/32			ENSP00000499323.1
MYO7A	ENST00000670577.1	n.*664G>C		3_prime_UTR_variant	28/32			ENSP00000499323.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000470 AC: 1 AN: 212904 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 115038

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000322

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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 AF: 6.94e-7 AC: 1 AN: 1440796 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 714426

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000239

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	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	D;.;.;D
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Uncertain	-0.054	T
MutationAssessor	Uncertain	2.2	M;.;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.0	D;D;D;D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.023	D;D;D;D
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.98	D;.;.;.
Vest4		0.70
MutPred		0.66		Gain of phosphorylation at T2030 (P = 0.1194);.;.;.;
MVP		0.88
MPC		0.14
ClinPred		0.97	D
GERP RS		3.7
Varity_R		0.97
gMVP		0.86

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: rs762258869; hg19: chr11-76922237;