10-100463200-G-T

Variant names:

• chr10-100463200-G-T
• NM_003393.4:c.32G>T

Variant summary

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

The NM_003393.4(WNT8B):​c.32G>T​(p.Cys11Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C11S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WNT8B NM_003393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

Genes affected

WNT8B (HGNC:12789): (Wnt family member 8B) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 95%, 86% and 71% amino acid identity to the mouse, zebrafish and Xenopus Wnt8B proteins, respectively. The expression patterns of the human and mouse genes appear identical and are restricted to the developing brain. The chromosomal location of this gene to 10q24 suggests it as a candidate gene for partial epilepsy. [provided by RefSeq, Jul 2008]

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=0.07615614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT8B	NM_003393.4	c.32G>T	p.Cys11Phe	missense_variant	Exon 1 of 6	ENST00000343737.6	NP_003384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT8B	ENST00000343737.6	c.32G>T	p.Cys11Phe	missense_variant	Exon 1 of 6	1	NM_003393.4	ENSP00000340677.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461548 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727080

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.63
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.4	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.11
Sift	Benign	0.38	T
Sift4G	Benign	0.71	T
Polyphen		0.0	B
Vest4		0.080
MutPred		0.41		Loss of catalytic residue at L12 (P = 0.0137);
MVP		0.43
MPC		1.2
ClinPred		0.084	T
GERP RS		4.7
Varity_R		0.073
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr10-102222957; COSMIC: COSV59326419;