Variant 9-15989-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP3BP4_Strong

The NM_001378090.1(WASHC1):c.1115C>G(p.Ala372Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 142,370 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 26)

Exomes 𝑓: 0.000068 ( 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: 8.27

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 -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 6: BayesDel_addAF, BayesDel_noAF, Cadd, MutationAssessor, phyloP100way_vertebrate, PrimateAI [when AlphaMissense, Dann, max_spliceai, MetaRNN was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.02524808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC1	NM_001378090.1 linkuse as main transcript	c.1115C>G	p.Ala372Gly	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.1115C>G	p.Ala372Gly	missense_variant	9/11		NM_001378090.1	ENSP00000512441.1	A8K0Z3
WASHC1	ENST00000442898.5 linkuse as main transcript	c.1115C>G	p.Ala372Gly	missense_variant	9/11	2		ENSP00000485627.1	A8K0Z3
WASHC1	ENST00000696150.1 linkuse as main transcript	n.1379C>G		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

142256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000205

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000220

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000262

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00826

AC:

982

AN:

118880

Hom.:

110

AF XY:

0.00776

AC XY:

502

AN XY:

64706

show subpopulations

Gnomad AFR exome

AF:

0.00989

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.00467

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00502

Gnomad FIN exome

AF:

0.00864

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.0117

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000675

AC:

AN:

1184794

Hom.:

Cov.:

AF XY:

0.0000656

AC XY:

AN XY:

594432

show subpopulations

Gnomad4 AFR exome

AF:

0.0000847

Gnomad4 AMR exome

AF:

0.0000784

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000398

Gnomad4 FIN exome

AF:

0.0000420

Gnomad4 NFE exome

AF:

0.0000768

Gnomad4 OTH exome

AF:

0.0000395

GnomAD4 genome

AF:

0.000204

AC:

AN:

142370

Hom.:

Cov.:

AF XY:

0.000245

AC XY:

AN XY:

69418

show subpopulations

Gnomad4 AFR

AF:

0.000218

Gnomad4 AMR

AF:

0.000205

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000220

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000262

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0380

Hom.:

ExAC

AF:

0.0000237

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 04, 2022

The c.1115C>G (p.A372G) 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 1115, causing the alanine (A) at amino acid position 372 to be replaced by a glycine (G). 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

0.16

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Benign

0.93

DEOGEN2

Benign

0.23

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.025

MutationAssessor

Pathogenic

3.5

PrimateAI

Pathogenic

0.79

Sift4G

Uncertain

0.054

Polyphen

1.0

Vest4

0.69

MVP

0.27

GERP RS

1.3

Varity_R

0.035

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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