rs782218928

Variant names:

• chr11-77179788-C-G
• rs782218928
• NM_000260.4:c.2421C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-77179788-C-G
• chr11-77179788-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000260.4(MYO7A):​c.2421C>G​(p.His807Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H807P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MYO7A NM_000260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10433951).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	NM_000260.4	MANE Select	c.2421C>G	p.His807Gln	missense	Exon 21 of 49	NP_000251.3
	MYO7A	NM_001127180.2		c.2421C>G	p.His807Gln	missense	Exon 21 of 49	NP_001120652.1
	MYO7A	NM_001369365.1		c.2388C>G	p.His796Gln	missense	Exon 22 of 50	NP_001356294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.2421C>G	p.His807Gln	missense	Exon 21 of 49	ENSP00000386331.3
	MYO7A	ENST00000458637.6	TSL:1	c.2421C>G	p.His807Gln	missense	Exon 21 of 49	ENSP00000392185.2
	MYO7A	ENST00000409619.6	TSL:1	c.2388C>G	p.His796Gln	missense	Exon 22 of 50	ENSP00000386635.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000668 AC: 1 AN: 149594 AF XY: 0.0000123

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000172

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398752 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690716

African (AFR) AF: 0.00 AC: 0 AN: 31804

American (AMR) AF: 0.00 AC: 0 AN: 36690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25220

East Asian (EAS) AF: 0.00 AC: 0 AN: 36062

South Asian (SAS) AF: 0.00 AC: 0 AN: 79520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5538

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081860

Other (OTH) AF: 0.0000172 AC: 1 AN: 58114

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.31
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.061
Sift	Benign	0.38	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.33		Loss of methylation at R804 (P = 0.0518)
MVP		0.63
MPC		0.085
ClinPred		0.22	T
GERP RS		3.3
PromoterAI		0.021	Neutral
Varity_R		0.099
gMVP		0.44
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs782218928; hg19: chr11-76890834;