Variant 9-16730-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001378090.1(WASHC1):c.1030G>A(p.Ala344Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.013 ( 0 hom., cov: 2)

Exomes 𝑓: 0.023 ( 749 hom. )

Failed GnomAD Quality Control

Consequence

WASHC1
NM_001378090.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.93

Variant links:

Genes affected

WASHC1 (HGNC:24361): (WASH complex subunit 1) Enables alpha-tubulin binding activity and ubiquitin protein ligase binding activity. Involved in several processes, including Arp2/3 complex-mediated actin nucleation; endosomal transport; and positive regulation of pseudopodium assembly. Located in early endosome. Part of WASH complex. Colocalizes with exocyst. [provided by Alliance of Genome Resources, Apr 2022]

WASHC1 links:

WASHC1 (HGNC:):

WASHC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019864291).

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0234 (5808/248720) while in subpopulation NFE AF= 0.0269 (4040/150220). AF 95% confidence interval is 0.0262. There are 749 homozygotes in gnomad4_exome. There are 2907 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 749 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC1	NM_001378090.1 linkuse as main transcript	c.1030G>A	p.Ala344Thr	missense_variant	8/11	ENST00000696149.1	NP_001365019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASHC1	ENST00000696149.1 linkuse as main transcript	c.1030G>A	p.Ala344Thr	missense_variant	8/11		NM_001378090.1	ENSP00000512441.1		A8K0Z3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

149

AN:

10944

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0201

Gnomad ASJ

AF:

0.00556

Gnomad EAS

AF:

0.00246

Gnomad SAS

AF:

0.00515

Gnomad FIN

AF:

0.0200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00123

AC:

AN:

36572

Hom.:

AF XY:

0.00134

AC XY:

AN XY:

18622

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00140

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00218

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0234

AC:

5808

AN:

248720

Hom.:

749

Cov.:

AF XY:

0.0219

AC XY:

2907

AN XY:

132778

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.00594

Gnomad4 EAS exome

AF:

0.00522

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.0516

Gnomad4 NFE exome

AF:

0.0269

Gnomad4 OTH exome

AF:

0.0238

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0134

AC:

147

AN:

10938

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

AN XY:

4464

show subpopulations

Gnomad4 AFR

AF:

0.0112

Gnomad4 AMR

AF:

0.0200

Gnomad4 ASJ

AF:

0.00556

Gnomad4 EAS

AF:

0.00250

Gnomad4 SAS

AF:

0.00532

Gnomad4 FIN

AF:

0.0200

Gnomad4 NFE

AF:

0.0144

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0125

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2022

The c.1030G>A (p.A344T) alteration is located in exon 8 (coding exon 7) of the WASH1 gene. This alteration results from a G to A substitution at nucleotide position 1030, causing the alanine (A) at amino acid position 344 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.029

DANN

Benign

0.94

DEOGEN2

Benign

0.019

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.26

MetaRNN

Benign

0.020

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.80

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.022

MVP

0.067

GERP RS

1.2

Varity_R

0.018

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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