rs111033476

Variant names:

• chr11-77207381-C-G
• rs111033476
• NM_000260.4:c.5835C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-77207381-C-G
• chr11-77207381-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000260.4(MYO7A):​c.5835C>G​(p.Leu1945Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L1945L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYO7A NM_000260.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=0.254 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	NM_000260.4	MANE Select	c.5835C>G	p.Leu1945Leu	synonymous	Exon 42 of 49	NP_000251.3
	MYO7A	NM_001127180.2		c.5721C>G	p.Leu1907Leu	synonymous	Exon 42 of 49	NP_001120652.1
	MYO7A	NM_001369365.1		c.5688C>G	p.Leu1896Leu	synonymous	Exon 43 of 50	NP_001356294.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.5835C>G	p.Leu1945Leu	synonymous	Exon 42 of 49	ENSP00000386331.3
	MYO7A	ENST00000458637.6	TSL:1	c.5721C>G	p.Leu1907Leu	synonymous	Exon 42 of 49	ENSP00000392185.2
	MYO7A	ENST00000409619.6	TSL:1	c.5688C>G	p.Leu1896Leu	synonymous	Exon 43 of 50	ENSP00000386635.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.5
DANN	Benign	0.74
PhyloP100		0.25

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: rs111033476; hg19: chr11-76918426;