Variant 9-15957-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001378090.1(WASHC1):c.1147A>G(p.Met383Val) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00091 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WASHC1
NM_001378090.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.01

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04962063).

BP6

Variant 9-15957-T-C is Benign according to our data. Variant chr9-15957-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3189540.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC1	NM_001378090.1 linkuse as main transcript	c.1147A>G	p.Met383Val	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.1147A>G	p.Met383Val	missense_variant	9/11		NM_001378090.1	ENSP00000512441.1	A8K0Z3
WASHC1	ENST00000442898.5 linkuse as main transcript	c.1147A>G	p.Met383Val	missense_variant	9/11	2		ENSP00000485627.1	A8K0Z3
WASHC1	ENST00000696150.1 linkuse as main transcript	n.1411A>G		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

318

AN:

122426

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00552

Gnomad AMI

AF:

0.00300

Gnomad AMR

AF:

0.00240

Gnomad ASJ

AF:

0.00101

Gnomad EAS

AF:

0.000609

Gnomad SAS

AF:

0.00122

Gnomad FIN

AF:

0.00369

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.00177

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000912

AC:

1036

AN:

1136030

Hom.:

Cov.:

AF XY:

0.000944

AC XY:

540

AN XY:

572080

show subpopulations

Gnomad4 AFR exome

AF:

0.00438

Gnomad4 AMR exome

AF:

0.000562

Gnomad4 ASJ exome

AF:

0.00179

Gnomad4 EAS exome

AF:

0.000325

Gnomad4 SAS exome

AF:

0.000961

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.000810

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00259

AC:

317

AN:

122468

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

153

AN XY:

59592

show subpopulations

Gnomad4 AFR

AF:

0.00547

Gnomad4 AMR

AF:

0.00240

Gnomad4 ASJ

AF:

0.00101

Gnomad4 EAS

AF:

0.000610

Gnomad4 SAS

AF:

0.00123

Gnomad4 FIN

AF:

0.00369

Gnomad4 NFE

AF:

0.00151

Gnomad4 OTH

AF:

0.00175

Alfa

AF:

0.00154

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.017

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.038

MetaRNN

Benign

0.050

MutationAssessor

Benign

-2.8

PrimateAI

Uncertain

0.76

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.15

MVP

0.23

GERP RS

1.3

Varity_R

0.14

gMVP

0.27

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