10-102744135-C-A

Variant names:

• chr10-102744135-C-A
• rs1170755396
• NM_001083913.2:c.82C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001083913.2(WBP1L):​c.82C>A​(p.Pro28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WBP1L NM_001083913.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.099696636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WBP1L	NM_001083913.2	c.82C>A	p.Pro28Thr	missense_variant	Exon 1 of 4	ENST00000448841.7	NP_001077382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WBP1L	ENST00000448841.7	c.82C>A	p.Pro28Thr	missense_variant	Exon 1 of 4	2	NM_001083913.2	ENSP00000414721.1
WBP1L	ENST00000647664.1	n.82C>A		non_coding_transcript_exon_variant	Exon 1 of 8			ENSP00000498131.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000139 AC: 2 AN: 144068 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 77632

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000830

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398326 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689728

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000560

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.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.012
Sift	Benign	0.27	T
Sift4G	Benign	0.53	T
Polyphen		0.29	B
Vest4		0.46
MutPred		0.15		Loss of catalytic residue at P28 (P = 0.0134);
MVP		0.043
MPC		0.79
ClinPred		0.92	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1170755396; hg19: chr10-104503892;