Variant 6-75915362-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004999.4(MYO6):c.*350T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 338,144 control chromosomes in the GnomAD database, including 24,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9713 hom., cov: 32)

Exomes 𝑓: 0.39 ( 14427 hom. )

Consequence

MYO6
NM_004999.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.434

Variant links:

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]

MYO6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-75915362-T-C is Benign according to our data. Variant chr6-75915362-T-C is described in ClinVar as [Benign]. Clinvar id is 358003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO6	NM_004999.4 linkuse as main transcript	c.*350T>C		3_prime_UTR_variant	35/35	ENST00000369977.8	NP_004990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO6	ENST00000369977.8 linkuse as main transcript	c.*350T>C		3_prime_UTR_variant	35/35	1	NM_004999.4	ENSP00000358994	A1	Q9UM54-1

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51693

AN:

151938

Hom.:

9686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.452

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.372

GnomAD4 exome

AF:

0.385

AC:

71658

AN:

186088

Hom.:

14427

Cov.:

AF XY:

0.382

AC XY:

38372

AN XY:

100352

show subpopulations

Gnomad4 AFR exome

AF:

0.175

Gnomad4 AMR exome

AF:

0.558

Gnomad4 ASJ exome

AF:

0.455

Gnomad4 EAS exome

AF:

0.393

Gnomad4 SAS exome

AF:

0.374

Gnomad4 FIN exome

AF:

0.396

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.377

GnomAD4 genome

AF:

0.340

AC:

51736

AN:

152056

Hom.:

9713

Cov.:

AF XY:

0.344

AC XY:

25554

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.481

Gnomad4 ASJ

AF:

0.452

Gnomad4 EAS

AF:

0.391

Gnomad4 SAS

AF:

0.382

Gnomad4 FIN

AF:

0.394

Gnomad4 NFE

AF:

0.381

Gnomad4 OTH

AF:

0.380

Alfa

AF:

0.384

Hom.:

10903

Bravo

AF:

0.343

Asia WGS

AF:

0.403

AC:

1398

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Autosomal recessive nonsyndromic hearing loss 37

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal dominant nonsyndromic hearing loss 22

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over