11-77208433-C-T

Position:

• chr11-77208433-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.5860C>T​(p.Leu1954Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1954I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYO7A NM_000260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.96

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.327644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.5860C>T	p.Leu1954Phe	missense_variant	43/49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.5860C>T	p.Leu1954Phe	missense_variant	43/49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.5746C>T	p.Leu1916Phe	missense_variant	43/49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.5713C>T	p.Leu1905Phe	missense_variant	44/50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.3286C>T	p.Leu1096Phe	missense_variant	23/29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.*458C>T		non_coding_transcript_exon_variant	26/32			ENSP00000499323.1
MYO7A	ENST00000670577.1	n.*458C>T		3_prime_UTR_variant	26/32			ENSP00000499323.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1457806 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 725126

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;.;.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	0.30	N;.;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.16	T;T;T;T
Sift4G	Benign	0.13	T;T;T;T
Vest4		0.20
MutPred		0.40		Loss of catalytic residue at L1954 (P = 0.0733);.;.;.;
MVP		0.78
MPC		0.092
ClinPred		0.65	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs948962; hg19: chr11-76919478;