Variant chr13-108785736-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001198950.3(MYO16):c.609T>A(p.Asp203Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 1,597,600 control chromosomes in the GnomAD database, including 2,996 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.033 ( 250 hom., cov: 33)

Exomes 𝑓: 0.042 ( 2746 hom. )

Consequence

MYO16
NM_001198950.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

MYO16 (HGNC:29822): (myosin XVI) This gene encodes an unconventional myosin protein. The encoded protein has been proposed to act as a serine/threonine phosphatase-1 targeting or regulatory subunit. Studies in a rat cell line suggest that this protein may regulate cell cycle progression. A variant within this gene may be associated with susceptibility to schizophrenia and elevated expression of this gene has been observed in the frontal cortex of human schizophrenia patients. [provided by RefSeq, Mar 2017]

MYO16 links:

MYO16 (HGNC:):

MYO16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015803277).

BP6

Variant 13-108785736-T-A is Benign according to our data. Variant chr13-108785736-T-A is described in ClinVar as [Benign]. Clinvar id is 3059259.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO16	NM_001198950.3 linkuse as main transcript	c.609T>A	p.Asp203Glu	missense_variant	5/35	ENST00000457511.7	NP_001185879.1	F8W883

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYO16	ENST00000457511.7 linkuse as main transcript	c.609T>A	p.Asp203Glu	missense_variant	5/35	1	NM_001198950.3	ENSP00000401633.3	F8W883
MYO16	ENST00000356711.7 linkuse as main transcript	c.543T>A	p.Asp181Glu	missense_variant	5/35	1		ENSP00000349145.2	Q9Y6X6-1
MYO16	ENST00000251041.10 linkuse as main transcript	c.543T>A	p.Asp181Glu	missense_variant	5/25	5		ENSP00000251041.5	Q9Y6X6-3
MYO16	ENST00000467639.1 linkuse as main transcript	n.613T>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0334

AC:

5082

AN:

152218

Hom.:

249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00779

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0328

Gnomad ASJ

AF:

0.0447

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.00828

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0290

Gnomad OTH

AF:

0.0325

GnomAD3 exomes

AF:

0.0528

AC:

12653

AN:

239740

Hom.:

829

AF XY:

0.0564

AC XY:

7313

AN XY:

129600

show subpopulations

Gnomad AFR exome

AF:

0.00857

Gnomad AMR exome

AF:

0.0323

Gnomad ASJ exome

AF:

0.0473

Gnomad EAS exome

AF:

0.230

Gnomad SAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.00861

Gnomad NFE exome

AF:

0.0265

Gnomad OTH exome

AF:

0.0425

GnomAD4 exome

AF:

0.0419

AC:

60532

AN:

1445264

Hom.:

2746

Cov.:

AF XY:

0.0441

AC XY:

31725

AN XY:

719240

show subpopulations

Gnomad4 AFR exome

AF:

0.00594

Gnomad4 AMR exome

AF:

0.0324

Gnomad4 ASJ exome

AF:

0.0462

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.00837

Gnomad4 NFE exome

AF:

0.0306

Gnomad4 OTH exome

AF:

0.0528

GnomAD4 genome

AF:

0.0333

AC:

5080

AN:

152336

Hom.:

250

Cov.:

AF XY:

0.0355

AC XY:

2641

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00782

Gnomad4 AMR

AF:

0.0326

Gnomad4 ASJ

AF:

0.0447

Gnomad4 EAS

AF:

0.238

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.00828

Gnomad4 NFE

AF:

0.0290

Gnomad4 OTH

AF:

0.0340

Alfa

AF:

0.0370

Hom.:

150

Bravo

AF:

0.0309

TwinsUK

AF:

0.0289

AC:

107

ALSPAC

AF:

0.0332

AC:

128

ESP6500AA

AF:

0.0111

AC:

ESP6500EA

AF:

0.0299

AC:

257

ExAC

AF:

0.0524

AC:

6360

Asia WGS

AF:

0.169

AC:

589

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MYO16-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.3

DANN

Benign

0.85

DEOGEN2

Benign

0.0011

T;T;.;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.46

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.63

N;.;N;N

REVEL

Benign

0.046

Sift

Benign

0.58

T;.;T;T

Sift4G

Benign

0.88

T;T;T;T

Polyphen

0.025

B;.;.;B

Vest4

0.085

MutPred

0.12

Gain of disorder (P = 0.2658);.;Gain of disorder (P = 0.2658);Gain of disorder (P = 0.2658);

MPC

0.18

ClinPred

0.0040

GERP RS

2.7

Varity_R

0.041

gMVP

0.12

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