Variant chr12-102046095-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016053.4(WASHC3):c.175A>G(p.Ile59Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WASHC3
NM_016053.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.60

Variant links:

Genes affected

WASHC3 (HGNC:24256): (WASH complex subunit 3) Predicted to be involved in actin filament polymerization and exocytosis. Part of WASH complex. [provided by Alliance of Genome Resources, Apr 2022]

WASHC3 links:

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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/exons	MANE	UniProt
WASHC3	NM_016053.4 linkuse as main transcript	c.175A>G	p.Ile59Val	missense_variant	3/7	ENST00000240079.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WASHC3	ENST00000240079.11 linkuse as main transcript	c.175A>G	p.Ile59Val	missense_variant	3/7	1	NM_016053.4	P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1445530

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718280

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 31, 2023

The c.175A>G (p.I59V) alteration is located in exon 3 (coding exon 3) of the CCDC53 gene. This alteration results from a A to G substitution at nucleotide position 175, causing the isoleucine (I) at amino acid position 59 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

Uncertain

0.45

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.041

T;.;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.0098

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Uncertain

-0.19

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.88

N;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.013

D;D;D

Sift4G

Uncertain

0.024

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.68

MutPred

0.62

Gain of catalytic residue at R58 (P = 0.0736);Gain of catalytic residue at R58 (P = 0.0736);.;

MVP

0.41

MPC

0.24

ClinPred

0.95

GERP RS

5.4

Varity_R

0.25

gMVP

0.50

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over