17-46872601-G-T

Variant names:

• chr17-46872601-G-T
• rs200969361
• NM_003396.3:c.162G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003396.3(WNT9B):​c.162G>T​(p.Gln54His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WNT9B NM_003396.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38096008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT9B	NM_003396.3	c.162G>T	p.Gln54His	missense_variant	Exon 2 of 4	ENST00000290015.7	NP_003387.1
WNT9B	NM_001320458.2	c.162G>T	p.Gln54His	missense_variant	Exon 2 of 5		NP_001307387.1
WNT9B	XM_011525178.3	c.180G>T	p.Gln60His	missense_variant	Exon 2 of 4		XP_011523480.1
LRRC37A2	XM_024450773.2	c.4810-176455G>T		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.162G>T	p.Gln54His	missense_variant	Exon 2 of 4	1	NM_003396.3	ENSP00000290015.2
WNT9B	ENST00000393461.2	c.162G>T	p.Gln54His	missense_variant	Exon 2 of 5	2		ENSP00000377105.2
WNT9B	ENST00000575372.5	c.180G>T	p.Gln60His	missense_variant	Exon 2 of 3	4		ENSP00000458192.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	.;T;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.85	.;L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.1	.;N;N
REVEL	Uncertain	0.43
Sift	Benign	0.56	.;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.80, 0.99	.;P;D
Vest4		0.56, 0.56
MutPred		0.63		.;Loss of MoRF binding (P = 0.1025);Loss of MoRF binding (P = 0.1025);
MVP		0.91
MPC		0.27
ClinPred		0.49	T
GERP RS		3.5
Varity_R		0.089
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs200969361; hg19: chr17-44949967;