chr9-14821-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001378090.1(WASHC1):​c.1384G>C​(p.Asp462His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D462N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

WASHC1
NM_001378090.1 missense

Scores

2
6
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.47
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WASHC1NM_001378090.1 linkc.1384G>C p.Asp462His missense_variant Exon 11 of 11 ENST00000696149.1 NP_001365019.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WASHC1ENST00000696149.1 linkc.1384G>C p.Asp462His missense_variant Exon 11 of 11 NM_001378090.1 ENSP00000512441.1 A8K0Z3
WASHC1ENST00000442898.5 linkc.1384G>C p.Asp462His missense_variant Exon 11 of 11 2 ENSP00000485627.1 A8K0Z3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
39
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Benign
23
DANN
Benign
0.90
DEOGEN2
Benign
0.27
T
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.92
D
MetaRNN
Uncertain
0.63
D
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Uncertain
0.66
T
Sift4G
Uncertain
0.0060
D
Polyphen
1.0
D
Vest4
0.42
MVP
0.32
GERP RS
1.2
Varity_R
0.059
gMVP
0.54

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.

Other links and lift over

dbSNP: rs761521000; hg19: chr9-14821; API