NM_003396.3:c.56C>T

Variant names:

• chr17-46851694-C-T
• rs2084848517
• NM_003396.3:c.56C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003396.3(WNT9B):​c.56C>T​(p.Ala19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000611 in 1,309,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: WNT9B NM_003396.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.335
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31536108).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003396.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT9B	NM_003396.3	MANE Select	c.56C>T	p.Ala19Val	missense	Exon 1 of 4	NP_003387.1	O14905
	WNT9B	NM_001320458.2		c.56C>T	p.Ala19Val	missense	Exon 1 of 5	NP_001307387.1	E7EPC3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT9B	ENST00000290015.7	TSL:1 MANE Select	c.56C>T	p.Ala19Val	missense	Exon 1 of 4	ENSP00000290015.2	O14905
	WNT9B	ENST00000393461.2	TSL:2	c.56C>T	p.Ala19Val	missense	Exon 1 of 5	ENSP00000377105.2	E7EPC3
	WNT9B	ENST00000575372.5	TSL:4	c.95+18254C>T		intron	N/A	ENSP00000458192.1	I3L0L8

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150870 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000487

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 AF: 0.00000518 AC: 6 AN: 1158656 Hom.: 0 Cov.: 31 AF XY: 0.00000891 AC XY: 5 AN XY: 561104

African (AFR) AF: 0.0000849 AC: 2 AN: 23562

American (AMR) AF: 0.00 AC: 0 AN: 11872

Ashkenazi Jewish (ASJ) AF: 0.0000624 AC: 1 AN: 16018

East Asian (EAS) AF: 0.00 AC: 0 AN: 26958

South Asian (SAS) AF: 0.00 AC: 0 AN: 38346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3518

European-Non Finnish (NFE) AF: 0.00000310 AC: 3 AN: 966428

Other (OTH) AF: 0.00 AC: 0 AN: 46836

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150870 Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1 AN XY: 73634

African (AFR) AF: 0.0000487 AC: 2 AN: 41094

American (AMR) AF: 0.00 AC: 0 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67634

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.65	D
M_CAP	Pathogenic	0.76	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.34
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.21
Sift	Benign	0.28	T
Sift4G	Benign	0.36	T
Polyphen		0.020	B
Vest4		0.22
MutPred		0.48		Loss of helix (P = 0.0444)
MVP		0.75
MPC		0.26
ClinPred		0.63	D
GERP RS		4.2
PromoterAI		0.010	Neutral
Varity_R		0.14
gMVP		0.38

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

Other links and lift over

dbSNP: rs2084848517; hg19: chr17-44929060;