rs3798425

Positions:

• chr6-75897833-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004999.4(MYO6):​c.3138-540C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,130 control chromosomes in the GnomAD database, including 5,575 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (5575 hom., cov: 33)
• Consequence: MYO6 NM_004999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO6	NM_004999.4	c.3138-540C>G		intron_variant		ENST00000369977.8	NP_004990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO6	ENST00000369977.8	c.3138-540C>G		intron_variant		1	NM_004999.4	ENSP00000358994.3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36752 AN: 152012 Hom.: 5576 Cov.: 33

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.241 AC: 36739 AN: 152130 Hom.: 5575 Cov.: 33 AF XY: 0.241 AC XY: 17897 AN XY: 74350

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.237

Alfa AF: 0.276 Hom.: 823

Bravo AF: 0.224

Asia WGS AF: 0.215 AC: 751 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	16
DANN	Benign	0.67

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: rs3798425; hg19: chr6-76607550;