chr17-46872756-T-G

Variant names:

• chr17-46872756-T-G
• rs4968281
• NM_003396.3:c.317T>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003396.3(WNT9B):​c.317T>G​(p.Met106Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 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. M106T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WNT9B NM_003396.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.834

Genes affected

WNT9B (HGNC:12779): (Wnt family member 9B) The WNT gene family consists of structurally related genes that 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. Study of its expression in the teratocarcinoma cell line NT2 suggests that it may be implicated in the early process of neuronal differentiation of NT2 cells induced by retinoic acid. This gene is clustered with WNT3, another family member, in the chromosome 17q21 region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05396372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT9B	NM_003396.3	c.317T>G	p.Met106Arg	missense_variant	Exon 2 of 4	ENST00000290015.7	NP_003387.1
WNT9B	NM_001320458.2	c.317T>G	p.Met106Arg	missense_variant	Exon 2 of 5		NP_001307387.1
WNT9B	XM_011525178.3	c.335T>G	p.Met112Arg	missense_variant	Exon 2 of 4		XP_011523480.1
LRRC37A2	XM_024450773.2	c.4810-176300T>G		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT9B	ENST00000290015.7	c.317T>G	p.Met106Arg	missense_variant	Exon 2 of 4	1	NM_003396.3	ENSP00000290015.2
WNT9B	ENST00000393461.2	c.317T>G	p.Met106Arg	missense_variant	Exon 2 of 5	2		ENSP00000377105.2
WNT9B	ENST00000575372.5	c.335T>G	p.Met112Arg	missense_variant	Exon 2 of 3	4		ENSP00000458192.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149824 Hom.: 0 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.00

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1441200 Hom.: 0 Cov.: 57 AF XY: 0.00 AC XY: 0 AN XY: 716438

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149824 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 73006

Gnomad4 AFR AF: 0.00

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.7
DANN	Benign	0.72
DEOGEN2	Benign	0.36	.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.20	N
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.054	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.78	.;N;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.090	.;N;N
REVEL	Benign	0.16
Sift	Benign	0.57	.;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.0, 0.010	.;B;B
Vest4		0.19, 0.18
MutPred		0.54		.;Gain of MoRF binding (P = 0.0365);Gain of MoRF binding (P = 0.0365);
MVP		0.35
MPC		0.39
ClinPred		0.037	T
GERP RS		-0.034
Varity_R		0.17
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4968281; hg19: chr17-44950122;