6-75749465-G-T

Position:

• chr6-75749465-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004999.4(MYO6):​c.-48+42G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 152,350 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (93 hom., cov: 32)
  • Exomes 𝑓: 0.050 (0 hom.)
• Consequence: MYO6 NM_004999.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0390

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-75749465-G-T is Benign according to our data. Variant chr6-75749465-G-T is described in ClinVar as [Benign]. Clinvar id is 1181480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0291 (4439/152290) while in subpopulation NFE AF= 0.0465 (3161/68002). AF 95% confidence interval is 0.0451. There are 93 homozygotes in gnomad4. There are 2118 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 93 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO6	NM_004999.4	c.-48+42G>T		intron_variant		ENST00000369977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO6	ENST00000369977.8	c.-48+42G>T		intron_variant		1	NM_004999.4	A1

Frequencies

GnomAD3 genomes AF: 0.0292 AC: 4438 AN: 152172 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.00784

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0465

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0500 AC: 3 AN: 60 Hom.: 0 Cov.: 0 AF XY: 0.0238 AC XY: 1 AN XY: 42

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0556

GnomAD4 genome AF: 0.0291 AC: 4439 AN: 152290 Hom.: 93 Cov.: 32 AF XY: 0.0284 AC XY: 2118 AN XY: 74472

Gnomad4 AFR AF: 0.00782

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0502

Gnomad4 NFE AF: 0.0465

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0199 Hom.: 15

Bravo AF: 0.0251

Asia WGS AF: 0.00549 AC: 20 AN: 3478

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

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.77

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: rs117153951; hg19: chr6-76459182;