chr17-46872574-G-C

Variant names:

• chr17-46872574-G-C
• rs372193837
• NM_003396.3:c.135G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_003396.3(WNT9B):​c.135G>C​(p.Pro45Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,599,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P45P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: WNT9B NM_003396.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.01
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-46872574-G-C is Benign according to our data. Variant chr17-46872574-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3045723.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-3.01 with no splicing effect.

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.135G>C	p.Pro45Pro	synonymous	Exon 2 of 4	NP_003387.1	O14905
	WNT9B	NM_001320458.2		c.135G>C	p.Pro45Pro	synonymous	Exon 2 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.135G>C	p.Pro45Pro	synonymous	Exon 2 of 4	ENSP00000290015.2	O14905
	WNT9B	ENST00000393461.2	TSL:2	c.135G>C	p.Pro45Pro	synonymous	Exon 2 of 5	ENSP00000377105.2	E7EPC3
	WNT9B	ENST00000575372.5	TSL:4	c.153G>C	p.Pro51Pro	synonymous	Exon 2 of 3	ENSP00000458192.1	I3L0L8

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000418 AC: 1 AN: 238964 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000931

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000262 AC: 38 AN: 1447756 Hom.: 0 Cov.: 31 AF XY: 0.0000306 AC XY: 22 AN XY: 718590

African (AFR) AF: 0.00 AC: 0 AN: 33196

American (AMR) AF: 0.00 AC: 0 AN: 43610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25336

East Asian (EAS) AF: 0.00 AC: 0 AN: 39338

South Asian (SAS) AF: 0.00 AC: 0 AN: 84400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5518

European-Non Finnish (NFE) AF: 0.0000335 AC: 37 AN: 1103756

Other (OTH) AF: 0.0000167 AC: 1 AN: 59702

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74380

African (AFR) AF: 0.0000482 AC: 2 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	WNT9B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0090
DANN	Benign	0.46
PhyloP100		-3.0

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: rs372193837; hg19: chr17-44949940;