6-75817304-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004999.4(MYO6):c.-47-197C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (0 hom., cov: 12)
  • Failed GnomAD Quality Control
• Consequence: MYO6 NM_004999.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.695

Genes affected

MYO6 (HGNC:7605): (myosin VI) This gene encodes a reverse-direction motor protein that moves toward the minus end of actin filaments and plays a role in intracellular vesicle and organelle transport. The protein consists of a motor domain containing an ATP- and an actin-binding site and a globular tail which interacts with other proteins. This protein maintains the structural integrity of inner ear hair cells and mutations in this gene cause non-syndromic autosomal dominant and recessive hearing loss. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-75817304-C-A is Benign according to our data. Variant chr6-75817304-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1195543.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO6	NM_004999.4	c.-47-197C>A		intron_variant		ENST00000369977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO6	ENST00000369977.8	c.-47-197C>A		intron_variant		1	NM_004999.4	A1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1793 AN: 61246 Hom.: 0 Cov.: 12 FAILED QC

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.0803

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.0359

Gnomad EAS AF: 0.00880

Gnomad SAS AF: 0.0198

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.0676

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.0303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0293 AC: 1798 AN: 61262 Hom.: 0 Cov.: 12 AF XY: 0.0293 AC XY: 848 AN XY: 28932

Gnomad4 AFR AF: 0.0194

Gnomad4 AMR AF: 0.0341

Gnomad4 ASJ AF: 0.0359

Gnomad4 EAS AF: 0.00884

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.0336

Gnomad4 NFE AF: 0.0367

Gnomad4 OTH AF: 0.0299

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs890890661; hg19: chr6-76527021;