Variant 10-50092198-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005751.3(WASHC2A):c.968T>C(p.Leu323Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)

Failed GnomAD Quality Control

Consequence

WASHC2A
NM_001005751.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.192

Variant links:

Genes affected

WASHC2A (HGNC:23416): (WASH complex subunit 2A) Predicted to enable phosphatidylinositol phosphate binding activity and retromer complex binding activity. Involved in protein localization to endosome. Located in cytosol and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

WASHC2A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038998485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC2A	NM_001005751.3 linkuse as main transcript	c.968T>C	p.Leu323Pro	missense_variant	11/31	ENST00000282633.10	NP_001005751.1	Q641Q2-1Q6P0Q7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASHC2A	ENST00000282633.10 linkuse as main transcript	c.968T>C	p.Leu323Pro	missense_variant	11/31	1	NM_001005751.3	ENSP00000282633.5		Q641Q2-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151748

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000659

AC:

AN:

151748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74110

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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 01, 2024

The c.968T>C (p.L323P) alteration is located in exon 11 (coding exon 11) of the FAM21A gene. This alteration results from a T to C substitution at nucleotide position 968, causing the leucine (L) at amino acid position 323 to be replaced by a proline (P). 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

0.060

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.18

DEOGEN2

Benign

0.011

.;T;T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.70

T;T;T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.039

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.65

N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.38

T;T;T;T

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.80

P;B;B;D

Vest4

0.10

MutPred

0.22

Gain of glycosylation at L323 (P = 0.0036);Gain of glycosylation at L323 (P = 0.0036);Gain of glycosylation at L323 (P = 0.0036);.;

MVP

0.043

ClinPred

0.068

GERP RS

0.34

Varity_R

0.10

gMVP

0.069

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

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