6-75817304-C-CAAAAA

Position:

• chr6-75817304-C-CAAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004999.4(MYO6):​c.-47-183_-47-179dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 62,962 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0051 (2 hom., cov: 31)
• Consequence: MYO6 NM_004999.4 intron
• Clinical Significance: Likely 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-CAAAAA is Benign according to our data. Variant chr6-75817304-C-CAAAAA is described in ClinVar as [Likely_benign]. Clinvar id is 1187980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00515 (324/62962) while in subpopulation AFR AF= 0.0155 (298/19242). AF 95% confidence interval is 0.014. There are 2 homozygotes in gnomad4. There are 153 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO6	NM_004999.4	c.-47-183_-47-179dup		intron_variant		ENST00000369977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO6	ENST00000369977.8	c.-47-183_-47-179dup		intron_variant		1	NM_004999.4	A1

Frequencies

GnomAD3 genomes AF: 0.00515 AC: 324 AN: 62942 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00109

Gnomad SAS AF: 0.00329

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000143

Gnomad OTH AF: 0.00591

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

GnomAD4 genome AF: 0.00515 AC: 324 AN: 62962 Hom.: 2 Cov.: 31 AF XY: 0.00516 AC XY: 153 AN XY: 29672

Gnomad4 AFR AF: 0.0155

Gnomad4 AMR AF: 0.00132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00109

Gnomad4 SAS AF: 0.00329

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000143

Gnomad4 OTH AF: 0.00584

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

Sep 19, 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;