Variant 10-102809937-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001083913.2(WBP1L):c.238T>C(p.Cys80Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,666 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

WBP1L
NM_001083913.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.99

Variant links:

Genes affected

WBP1L (HGNC:23510): (WW domain binding protein 1 like) Predicted to enable ubiquitin protein ligase binding activity. Predicted to act upstream of or within CXCL12-activated CXCR4 signaling pathway; hemopoiesis; and positive regulation of protein ubiquitination. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

WBP1L links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WBP1L	NM_001083913.2 linkuse as main transcript	c.238T>C	p.Cys80Arg	missense_variant	3/4	ENST00000448841.7	NP_001077382.1	Q9NX94-2
WBP1L	NM_017787.5 linkuse as main transcript	c.175T>C	p.Cys59Arg	missense_variant	3/4		NP_060257.4	Q9NX94-1
WBP1L	XM_011539913.3 linkuse as main transcript	c.211T>C	p.Cys71Arg	missense_variant	3/4		XP_011538215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WBP1L	ENST00000448841.7 linkuse as main transcript	c.238T>C	p.Cys80Arg	missense_variant	3/4	2	NM_001083913.2	ENSP00000414721.1	Q9NX94-2
WBP1L	ENST00000369889.5 linkuse as main transcript	c.175T>C	p.Cys59Arg	missense_variant	3/4	1		ENSP00000358905.4	Q9NX94-1
WBP1L	ENST00000647664.1 linkuse as main transcript	n.238T>C		non_coding_transcript_exon_variant	3/8			ENSP00000498131.1	A0A3B3IU90

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727158

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:

8.99e-7

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

Apr 09, 2024

The c.238T>C (p.C80R) alteration is located in exon 3 (coding exon 3) of the WBP1L gene. This alteration results from a T to C substitution at nucleotide position 238, causing the cysteine (C) at amino acid position 80 to be replaced by an arginine (R). 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

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.080

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Uncertain

-0.23

MutationAssessor

Pathogenic

3.0

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-11

D;D

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;D

Vest4

0.95

MutPred

0.90

.;Gain of MoRF binding (P = 0.0134);

MVP

0.33

MPC

1.3

ClinPred

1.0

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.98

gMVP

0.95

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