Variant chr4-48991463-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_025087.3(CWH43):c.245C>T(p.Ala82Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A82T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CWH43
NM_025087.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

CWH43 (HGNC:26133): (cell wall biogenesis 43 C-terminal homolog) Predicted to be involved in GPI anchor biosynthetic process. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

CWH43 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.789

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CWH43	NM_025087.3 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant	3/16	ENST00000226432.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CWH43	ENST00000226432.9 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant	3/16	1	NM_025087.3	P1
CWH43	ENST00000513409.1 linkuse as main transcript	c.164C>T	p.Ala55Val	missense_variant	3/16	2
CWH43	ENST00000514053.6 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant, NMD_transcript_variant	3/14	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727180

show subpopulations

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:

0.00000719

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

Dec 20, 2021

The c.245C>T (p.A82V) alteration is located in exon 3 (coding exon 3) of the CWH43 gene. This alteration results from a C to T substitution at nucleotide position 245, causing the alanine (A) at amino acid position 82 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

Benign

0.098

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.0067

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.20

Sift

Benign

0.15

T;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.99

D;.

Vest4

0.52

MutPred

0.78

Loss of glycosylation at P87 (P = 0.0471);.;

MVP

0.56

MPC

0.14

ClinPred

0.90

GERP RS

4.5

Varity_R

0.13

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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