Variant 9-16013-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.1091C>G(p.Thr364Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000842 in 144,890 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00030 ( 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: 2.18

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1715669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC1	NM_001378090.1 linkuse as main transcript	c.1091C>G	p.Thr364Ser	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.1091C>G	p.Thr364Ser	missense_variant	9/11		NM_001378090.1	ENSP00000512441.1	A8K0Z3
WASHC1	ENST00000442898.5 linkuse as main transcript	c.1091C>G	p.Thr364Ser	missense_variant	9/11	2		ENSP00000485627.1	A8K0Z3
WASHC1	ENST00000696150.1 linkuse as main transcript	n.1355C>G		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.000843

AC:

122

AN:

144772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000291

Gnomad AMI

AF:

0.00845

Gnomad AMR

AF:

0.000679

Gnomad ASJ

AF:

0.00213

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00313

Gnomad FIN

AF:

0.000290

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00105

Gnomad OTH

AF:

0.000511

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000303

AC:

381

AN:

1257414

Hom.:

Cov.:

AF XY:

0.000317

AC XY:

199

AN XY:

627552

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000787

Gnomad4 ASJ exome

AF:

0.000754

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000857

Gnomad4 FIN exome

AF:

0.0000624

Gnomad4 NFE exome

AF:

0.000277

Gnomad4 OTH exome

AF:

0.000377

GnomAD4 genome

AF:

0.000842

AC:

122

AN:

144890

Hom.:

Cov.:

AF XY:

0.000948

AC XY:

AN XY:

70684

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.000678

Gnomad4 ASJ

AF:

0.00213

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00313

Gnomad4 FIN

AF:

0.000290

Gnomad4 NFE

AF:

0.00105

Gnomad4 OTH

AF:

0.000506

Alfa

AF:

0.00135

Hom.:

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

Apr 08, 2022

The c.1091C>G (p.T364S) 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 1091, causing the threonine (T) at amino acid position 364 to be replaced by a serine (S). 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

0.087

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.017

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.48

MetaRNN

Benign

0.17

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.79

Sift4G

Benign

0.99

Polyphen

0.11

Vest4

0.13

MVP

0.23

GERP RS

1.3

Varity_R

0.049

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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