Variant 9-15996-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001378090.1(WASHC1):c.1108C>T(p.Arg370Cys) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000031 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WASHC1
NM_001378090.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

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 Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.947

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC1	NM_001378090.1 linkuse as main transcript	c.1108C>T	p.Arg370Cys	missense_variant	9/11	ENST00000696149.1	NP_001365019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WASHC1	ENST00000696149.1 linkuse as main transcript	c.1108C>T	p.Arg370Cys	missense_variant	9/11		NM_001378090.1	ENSP00000512441.1	A8K0Z3
WASHC1	ENST00000442898.5 linkuse as main transcript	c.1108C>T	p.Arg370Cys	missense_variant	9/11	2		ENSP00000485627.1	A8K0Z3
WASHC1	ENST00000696150.1 linkuse as main transcript	n.1372C>T		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.0000415

AC:

AN:

144704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000538

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000216

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000453

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000246

AC:

AN:

121916

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66062

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000191

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000212

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000306

AC:

AN:

1207858

Hom.:

Cov.:

AF XY:

0.0000314

AC XY:

AN XY:

605208

show subpopulations

Gnomad4 AFR exome

AF:

0.0000413

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000162

Gnomad4 SAS exome

AF:

0.0000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000276

Gnomad4 OTH exome

AF:

0.0000195

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000414

AC:

AN:

144818

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70646

show subpopulations

Gnomad4 AFR

AF:

0.0000537

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000216

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000454

Gnomad4 OTH

AF:

0.00

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

Aug 04, 2023

The c.1108C>T (p.R370C) alteration is located in exon 9 (coding exon 8) of the WASH1 gene. This alteration results from a C to T substitution at nucleotide position 1108, causing the arginine (R) at amino acid position 370 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

0.10

BayesDel_addAF

Pathogenic

0.52

BayesDel_noAF

Pathogenic

0.51

CADD

Pathogenic

DANN

Benign

0.94

DEOGEN2

Benign

0.35

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.92

MetaRNN

Pathogenic

0.95

MutationAssessor

Pathogenic

3.5

PrimateAI

Pathogenic

0.87

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.95

MVP

0.58

GERP RS

1.3

Varity_R

0.11

gMVP

0.55

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