Variant chr12-105111242-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_015275.3(WASHC4):c.179A>G(p.Asn60Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000814 in 1,609,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

WASHC4
NM_015275.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.84

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 -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0082834065).

BP6

Variant 12-105111242-A-G is Benign according to our data. Variant chr12-105111242-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 747204.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000144 (22/152330) while in subpopulation EAS AF= 0.00328 (17/5188). AF 95% confidence interval is 0.00209. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WASHC4	NM_015275.3 linkuse as main transcript	c.179A>G	p.Asn60Ser	missense_variant	2/33	ENST00000332180.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WASHC4	ENST00000332180.10 linkuse as main transcript	c.179A>G	p.Asn60Ser	missense_variant	2/33	1	NM_015275.3	A1	Q2M389-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000346

AC:

AN:

248636

Hom.:

AF XY:

0.000319

AC XY:

AN XY:

135000

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00395

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0000474

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000748

AC:

109

AN:

1457336

Hom.:

Cov.:

AF XY:

0.0000827

AC XY:

AN XY:

725266

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.000221

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.0000253

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.000144

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.000340

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.0019

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.066

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0022

MetaRNN

Benign

0.0083

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.72

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.36

N;.

REVEL

Benign

0.099

Sift

Benign

0.69

T;.

Sift4G

Benign

0.82

T;T

Polyphen

0.0

B;.

Vest4

0.20

MVP

0.21

MPC

0.14

ClinPred

0.014

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.20

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