Variant 12-105111175-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000332180.10(WASHC4):c.112T>C(p.Tyr38His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,605,798 control chromosomes in the GnomAD database, including 386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.015 ( 18 hom., cov: 33)

Exomes 𝑓: 0.020 ( 368 hom. )

Consequence

WASHC4
ENST00000332180.10 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.86

Variant links:

Genes affected

WASHC4 (HGNC:29174): (WASH complex subunit 4) This gene encodes a component of the WASH complex, which functions in the intracellular transport of endosomes. Mutations in this gene have been detected in individuals with autosomal recessive cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

WASHC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053884387).

BP6

Variant 12-105111175-T-C is Benign according to our data. Variant chr12-105111175-T-C is described in ClinVar as [Benign]. Clinvar id is 3055677.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0154 (2342/152284) while in subpopulation NFE AF= 0.0231 (1569/67992). AF 95% confidence interval is 0.0221. There are 18 homozygotes in gnomad4. There are 1124 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC4	NM_015275.3 linkuse as main transcript	c.112T>C	p.Tyr38His	missense_variant	2/33	ENST00000332180.10	NP_056090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASHC4	ENST00000332180.10 linkuse as main transcript	c.112T>C	p.Tyr38His	missense_variant	2/33	1	NM_015275.3	ENSP00000328062	A1	Q2M389-1

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2342

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00408

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00496

Gnomad FIN

AF:

0.0306

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0231

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0149

AC:

3701

AN:

248980

Hom.:

AF XY:

0.0149

AC XY:

2007

AN XY:

135146

show subpopulations

Gnomad AFR exome

AF:

0.00304

Gnomad AMR exome

AF:

0.00889

Gnomad ASJ exome

AF:

0.00725

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00804

Gnomad FIN exome

AF:

0.0293

Gnomad NFE exome

AF:

0.0204

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0202

AC:

29388

AN:

1453514

Hom.:

368

Cov.:

AF XY:

0.0197

AC XY:

14289

AN XY:

723626

show subpopulations

Gnomad4 AFR exome

AF:

0.00288

Gnomad4 AMR exome

AF:

0.00953

Gnomad4 ASJ exome

AF:

0.00736

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00856

Gnomad4 FIN exome

AF:

0.0283

Gnomad4 NFE exome

AF:

0.0228

Gnomad4 OTH exome

AF:

0.0193

GnomAD4 genome

AF:

0.0154

AC:

2342

AN:

152284

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1124

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00407

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0306

Gnomad4 NFE

AF:

0.0231

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0202

Hom.:

Bravo

AF:

0.0134

TwinsUK

AF:

0.0189

AC:

ALSPAC

AF:

0.0223

AC:

ESP6500AA

AF:

0.00414

AC:

ESP6500EA

AF:

0.0191

AC:

155

ExAC

AF:

0.0148

AC:

1788

Asia WGS

AF:

0.00404

AC:

AN:

3476

EpiCase

AF:

0.0211

EpiControl

AF:

0.0181

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

WASHC4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 05, 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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0051

T;T

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.14

Sift

Benign

0.38

T;.

Sift4G

Benign

0.43

T;T

Polyphen

0.30

B;.

Vest4

0.48

MPC

0.41

ClinPred

0.047

GERP RS

5.6

Varity_R

0.32

gMVP

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

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