Variant 9-16032-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001378090.1(WASHC1):c.1072C>T(p.Pro358Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000629 in 147,898 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00041 ( 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: 6.58

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC1	NM_001378090.1 linkuse as main transcript	c.1072C>T	p.Pro358Ser	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.1072C>T	p.Pro358Ser	missense_variant	9/11		NM_001378090.1	ENSP00000512441.1	A8K0Z3
WASHC1	ENST00000442898.5 linkuse as main transcript	c.1072C>T	p.Pro358Ser	missense_variant	9/11	2		ENSP00000485627.1	A8K0Z3
WASHC1	ENST00000696150.1 linkuse as main transcript	n.1336C>T		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.000629

AC:

AN:

147784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000255

Gnomad AMI

AF:

0.00465

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00195

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000265

AC:

AN:

113026

Hom.:

AF XY:

0.0000495

AC XY:

AN XY:

60612

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000405

AC:

530

AN:

1307344

Hom.:

Cov.:

AF XY:

0.000429

AC XY:

279

AN XY:

650704

show subpopulations

Gnomad4 AFR exome

AF:

0.000178

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000818

Gnomad4 NFE exome

AF:

0.000475

Gnomad4 OTH exome

AF:

0.000237

GnomAD4 genome

AF:

0.000629

AC:

AN:

147898

Hom.:

Cov.:

AF XY:

0.000706

AC XY:

AN XY:

72190

show subpopulations

Gnomad4 AFR

AF:

0.000254

Gnomad4 AMR

AF:

0.000199

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00195

Gnomad4 NFE

AF:

0.000839

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000735

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 20, 2023

The c.1072C>T (p.P358S) alteration is located in exon 9 (coding exon 8) of the WASH1 gene. This alteration results from a C to T substitution at nucleotide position 1072, causing the proline (P) at amino acid position 358 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

0.10

BayesDel_addAF

Benign

0.0079

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.097

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

MetaRNN

Uncertain

0.56

MutationAssessor

Uncertain

2.8

PrimateAI

Pathogenic

0.85

Sift4G

Benign

0.067

Polyphen

1.0

Vest4

0.54

MVP

0.35

GERP RS

1.3

Varity_R

0.063

gMVP

0.42

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