Variant 9-16026-C-T 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.1078G>A(p.Gly360Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000757 in 143,962 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00076 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00024 ( 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: 0.741

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=0.010076553).

BP6

Variant 9-16026-C-T is Benign according to our data. Variant chr9-16026-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3189535.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.1078G>A	p.Gly360Ser	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.1078G>A	p.Gly360Ser	missense_variant	9/11		NM_001378090.1	ENSP00000512441.1	A8K0Z3
WASHC1	ENST00000442898.5 linkuse as main transcript	c.1078G>A	p.Gly360Ser	missense_variant	9/11	2		ENSP00000485627.1	A8K0Z3
WASHC1	ENST00000696150.1 linkuse as main transcript	n.1342G>A		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.000758

AC:

109

AN:

143856

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00180

Gnomad AMI

AF:

0.00117

Gnomad AMR

AF:

0.000407

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000992

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0000983

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000228

Gnomad OTH

AF:

0.000509

GnomAD3 exomes

AF:

0.000322

AC:

AN:

114790

Hom.:

AF XY:

0.000308

AC XY:

AN XY:

61640

show subpopulations

Gnomad AFR exome

AF:

0.00560

Gnomad AMR exome

AF:

0.0000482

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000618

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000244

AC:

313

AN:

1283456

Hom.:

Cov.:

AF XY:

0.000266

AC XY:

170

AN XY:

639174

show subpopulations

Gnomad4 AFR exome

AF:

0.00283

Gnomad4 AMR exome

AF:

0.000133

Gnomad4 ASJ exome

AF:

0.000289

Gnomad4 EAS exome

AF:

0.0000545

Gnomad4 SAS exome

AF:

0.000926

Gnomad4 FIN exome

AF:

0.000211

Gnomad4 NFE exome

AF:

0.000119

Gnomad4 OTH exome

AF:

0.000427

GnomAD4 genome

AF:

0.000757

AC:

109

AN:

143962

Hom.:

Cov.:

AF XY:

0.000798

AC XY:

AN XY:

70194

show subpopulations

Gnomad4 AFR

AF:

0.00179

Gnomad4 AMR

AF:

0.000407

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000994

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.0000983

Gnomad4 NFE

AF:

0.000228

Gnomad4 OTH

AF:

0.000503

Alfa

AF:

0.000742

Hom.:

ExAC

AF:

0.0000620

AC:

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

May 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

0.079

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.019

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.70

MetaRNN

Benign

0.010

MutationAssessor

Benign

-0.89

PrimateAI

Uncertain

0.69

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.14

MVP

0.22

GERP RS

-1.5

Varity_R

0.031

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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