rs7927472

Variant names:

• chr11-77199721-C-A
• rs7927472
• NM_000260.4:c.4755C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-77199721-C-A
• chr11-77199721-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000260.4(MYO7A):​c.4755C>A​(p.Ser1585Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. S1585S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO7A NM_000260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.84
• Publications: 22 publications found

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 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
• Usher syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, PanelApp Australia
• Usher syndrome type 1B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant nonsyndromic hearing loss 11

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Usher syndrome type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33770156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.4755C>A	p.Ser1585Arg	missense_variant	Exon 35 of 49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.4755C>A	p.Ser1585Arg	missense_variant	Exon 35 of 49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.4641C>A	p.Ser1547Arg	missense_variant	Exon 35 of 49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.4608C>A	p.Ser1536Arg	missense_variant	Exon 36 of 50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.2184C>A	p.Ser728Arg	missense_variant	Exon 15 of 29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.2595C>A		non_coding_transcript_exon_variant	Exon 18 of 32			ENSP00000499323.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;.;.;T
Eigen	Benign	0.079
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	D;D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.3	L;.;.;.
PhyloP100		2.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.022	D;D;D;D
Sift4G	Benign	0.58	T;T;T;T
Vest4		0.38
ClinPred		0.85	D
GERP RS		4.0
Varity_R		0.34
gMVP		0.19
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7927472; hg19: chr11-76910766;