rs759614902

Positions:

• chr11-77211335-C-A
• chr11-77211335-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000260.4(MYO7A):​c.6235C>A​(p.Arg2079Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MYO7A NM_000260.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00003025
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=0.274 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.6235C>A	p.Arg2079Arg	splice_region_variant, synonymous_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.6235C>A	p.Arg2079Arg	splice_region_variant, synonymous_variant	45/49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.6121C>A	p.Arg2041Arg	splice_region_variant, synonymous_variant	45/49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.6088C>A	p.Arg2030Arg	splice_region_variant, synonymous_variant	46/50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.3661C>A	p.Arg1221Arg	splice_region_variant, synonymous_variant	25/29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.*807C>A		splice_region_variant, non_coding_transcript_exon_variant	28/32			ENSP00000499323.1
MYO7A	ENST00000670577.1	n.*807C>A		3_prime_UTR_variant	28/32			ENSP00000499323.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1425052 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 705104

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: 9.14e-7

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
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000030
dbscSNV1_RF	Benign	0.018
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: rs759614902; hg19: chr11-76922380;