Variant 12-102044181-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016053.4(WASHC3):c.248C>A(p.Thr83Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000536 in 1,608,990 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 5 hom. )

Consequence

WASHC3
NM_016053.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0089429915).

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WASHC3	NM_016053.4 linkuse as main transcript	c.248C>A	p.Thr83Lys	missense_variant	4/7	ENST00000240079.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WASHC3	ENST00000240079.11 linkuse as main transcript	c.248C>A	p.Thr83Lys	missense_variant	4/7	1	NM_016053.4	P4

Frequencies

GnomAD3 genomes

AF:

0.000677

AC:

103

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000584

AC:

143

AN:

244950

Hom.:

AF XY:

0.000573

AC XY:

AN XY:

132720

show subpopulations

Gnomad AFR exome

AF:

0.000264

Gnomad AMR exome

AF:

0.000708

Gnomad ASJ exome

AF:

0.00431

Gnomad EAS exome

AF:

0.0000566

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000576

Gnomad OTH exome

AF:

0.000505

GnomAD4 exome

AF:

0.000521

AC:

759

AN:

1456714

Hom.:

Cov.:

AF XY:

0.000534

AC XY:

387

AN XY:

724536

show subpopulations

Gnomad4 AFR exome

AF:

0.000451

Gnomad4 AMR exome

AF:

0.000676

Gnomad4 ASJ exome

AF:

0.00522

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000937

Gnomad4 FIN exome

AF:

0.0000751

Gnomad4 NFE exome

AF:

0.000405

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000676

AC:

103

AN:

152276

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000394

Hom.:

Bravo

AF:

0.000876

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000723

AC:

ExAC

AF:

0.000588

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

Nov 21, 2022

The c.248C>A (p.T83K) alteration is located in exon 4 (coding exon 4) of the CCDC53 gene. This alteration results from a C to A substitution at nucleotide position 248, causing the threonine (T) at amino acid position 83 to be replaced by a lysine (K). 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

-0.50

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.039

T;.;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0089

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.90

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.53

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0080

B;B;.

Vest4

0.18

MVP

0.085

MPC

0.056

ClinPred

0.021

GERP RS

2.1

Varity_R

0.13

gMVP

0.39

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