Variant 9-15942-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001378090.1(WASHC1):c.1162C>G(p.Leu388Val) 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0051 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0048 ( 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: 1.78

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10249156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC1	NM_001378090.1 linkuse as main transcript	c.1162C>G	p.Leu388Val	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.1162C>G	p.Leu388Val	missense_variant	9/11		NM_001378090.1	ENSP00000512441.1	A8K0Z3
WASHC1	ENST00000442898.5 linkuse as main transcript	c.1162C>G	p.Leu388Val	missense_variant	9/11	2		ENSP00000485627.1	A8K0Z3
WASHC1	ENST00000696150.1 linkuse as main transcript	n.1426C>G		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

541

AN:

106720

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00757

Gnomad AMI

AF:

0.00919

Gnomad AMR

AF:

0.00669

Gnomad ASJ

AF:

0.00225

Gnomad EAS

AF:

0.00467

Gnomad SAS

AF:

0.00610

Gnomad FIN

AF:

0.00453

Gnomad MID

AF:

0.00439

Gnomad NFE

AF:

0.00384

Gnomad OTH

AF:

0.00333

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00477

AC:

5678

AN:

1189192

Hom.:

Cov.:

AF XY:

0.00512

AC XY:

3048

AN XY:

594756

show subpopulations

Gnomad4 AFR exome

AF:

0.0155

Gnomad4 AMR exome

AF:

0.00656

Gnomad4 ASJ exome

AF:

0.00637

Gnomad4 EAS exome

AF:

0.0108

Gnomad4 SAS exome

AF:

0.0131

Gnomad4 FIN exome

AF:

0.00667

Gnomad4 NFE exome

AF:

0.00331

Gnomad4 OTH exome

AF:

0.00620

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00507

AC:

541

AN:

106760

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

274

AN XY:

51906

show subpopulations

Gnomad4 AFR

AF:

0.00760

Gnomad4 AMR

AF:

0.00677

Gnomad4 ASJ

AF:

0.00225

Gnomad4 EAS

AF:

0.00469

Gnomad4 SAS

AF:

0.00554

Gnomad4 FIN

AF:

0.00453

Gnomad4 NFE

AF:

0.00384

Gnomad4 OTH

AF:

0.00329

Alfa

AF:

0.0148

Hom.:

ExAC

AF:

0.0000305

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

Oct 18, 2021

The c.1162C>G (p.L388V) alteration is located in exon 9 (coding exon 8) of the WASH1 gene. This alteration results from a C to G substitution at nucleotide position 1162, causing the leucine (L) at amino acid position 388 to be replaced by a valine (V). 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

0.072

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.042

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.67

MetaRNN

Benign

0.10

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.74

Sift4G

Benign

0.55

Polyphen

0.016

Vest4

0.31

MVP

0.25

GERP RS

1.3

Varity_R

0.059

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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