Variant 9-14887-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001378090.1(WASHC1):c.1318C>T(p.Arg440Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000934 in 1,360,370 control chromosomes in the GnomAD database, including 11 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00010 ( 1 hom., cov: 24)

Exomes 𝑓: 0.000092 ( 10 hom. )

Consequence

WASHC1
NM_001378090.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC1	NM_001378090.1 linkuse as main transcript	c.1318C>T	p.Arg440Cys	missense_variant	11/11	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.1318C>T	p.Arg440Cys	missense_variant	11/11		NM_001378090.1	ENSP00000512441.1		A8K0Z3
WASHC1	ENST00000442898.5 linkuse as main transcript	c.1318C>T	p.Arg440Cys	missense_variant	11/11	2		ENSP00000485627.1		A8K0Z3

Frequencies

GnomAD3 genomes

AF:

0.000104

AC:

AN:

124590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000832

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

183762

Hom.:

AF XY:

0.0000200

AC XY:

AN XY:

100198

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000356

Gnomad ASJ exome

AF:

0.000267

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000361

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000923

AC:

114

AN:

1235732

Hom.:

Cov.:

AF XY:

0.0000843

AC XY:

AN XY:

616878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00116

Gnomad4 EAS exome

AF:

0.0000278

Gnomad4 SAS exome

AF:

0.0000670

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000795

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.000104

AC:

AN:

124638

Hom.:

Cov.:

AF XY:

0.0000988

AC XY:

AN XY:

60734

show subpopulations

Gnomad4 AFR

AF:

0.0000726

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00196

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000833

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000145

Hom.:

ExAC

AF:

0.0000727

AC:

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

Nov 10, 2024

The c.1318C>T (p.R440C) alteration is located in exon 11 (coding exon 10) of the WASH1 gene. This alteration results from a C to T substitution at nucleotide position 1318, causing the arginine (R) at amino acid position 440 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.21

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.94

MetaRNN

Uncertain

0.56

MutationAssessor

Pathogenic

3.2

PrimateAI

Uncertain

0.77

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.62

MVP

0.53

GERP RS

0.15

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.14

gMVP

0.33

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