6-75817304-C-CAAAA

Position:

• chr6-75817304-C-CAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000369977.8(MYO6):​c.-47-182_-47-179dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 62,818 control chromosomes in the GnomAD database, including 86 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.043 (86 hom., cov: 31)
• Consequence: MYO6 ENST00000369977.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.194

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 6-75817304-C-CAAAA is Benign according to our data. Variant chr6-75817304-C-CAAAA is described in ClinVar as [Benign]. Clinvar id is 1287413.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO6	NM_004999.4	c.-47-182_-47-179dup		intron_variant		ENST00000369977.8	NP_004990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO6	ENST00000369977.8	c.-47-182_-47-179dup		intron_variant		1	NM_004999.4	ENSP00000358994	A1

Frequencies

GnomAD3 genomes AF: 0.0429 AC: 2692 AN: 62798 Hom.: 87 Cov.: 31

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0139

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.0766

Gnomad MID AF: 0.0395

Gnomad NFE AF: 0.00367

Gnomad OTH AF: 0.0284

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

GnomAD4 genome AF: 0.0429 AC: 2698 AN: 62818 Hom.: 86 Cov.: 31 AF XY: 0.0445 AC XY: 1318 AN XY: 29600

Gnomad4 AFR AF: 0.0835

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0139

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.0217

Gnomad4 FIN AF: 0.0766

Gnomad4 NFE AF: 0.00367

Gnomad4 OTH AF: 0.0280

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs759910571; hg19: chr6-76527021;