Variant 9-15962-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001378090.1(WASHC1):c.1142G>A(p.Arg381His) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 136,300 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000082 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

WASHC1
NM_001378090.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC1	NM_001378090.1 linkuse as main transcript	c.1142G>A	p.Arg381His	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.1142G>A	p.Arg381His	missense_variant	9/11		NM_001378090.1	ENSP00000512441.1	A8K0Z3
WASHC1	ENST00000442898.5 linkuse as main transcript	c.1142G>A	p.Arg381His	missense_variant	9/11	2		ENSP00000485627.1	A8K0Z3
WASHC1	ENST00000696150.1 linkuse as main transcript	n.1406G>A		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.000110

AC:

AN:

136218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000151

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000705

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000226

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000126

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000892

AC:

AN:

134458

Hom.:

AF XY:

0.000109

AC XY:

AN XY:

73082

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000444

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000845

Gnomad SAS exome

AF:

0.000320

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000723

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000824

AC:

AN:

1140818

Hom.:

Cov.:

AF XY:

0.0000834

AC XY:

AN XY:

575600

show subpopulations

Gnomad4 AFR exome

AF:

0.000728

Gnomad4 AMR exome

AF:

0.000126

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000294

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000545

Gnomad4 OTH exome

AF:

0.0000819

GnomAD4 genome

AF:

0.000110

AC:

AN:

136300

Hom.:

Cov.:

AF XY:

0.0000754

AC XY:

AN XY:

66298

show subpopulations

Gnomad4 AFR

AF:

0.000151

Gnomad4 AMR

AF:

0.0000704

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000227

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000126

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000612

Hom.:

ExAC

AF:

0.0000533

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

Feb 21, 2024

The c.1142G>A (p.R381H) alteration is located in exon 9 (coding exon 8) of the WASH1 gene. This alteration results from a G to A substitution at nucleotide position 1142, causing the arginine (R) at amino acid position 381 to be replaced by a histidine (H). 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

0.075

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.21

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

MetaRNN

Uncertain

0.74

MutationAssessor

Pathogenic

2.9

PrimateAI

Uncertain

0.75

Sift4G

Benign

0.068

Polyphen

1.0

Vest4

0.78

MVP

0.26

GERP RS

1.3

Varity_R

0.035

gMVP

0.44

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