NM_003396.3:c.24C>G

Variant names:

• chr17-46851662-C-G
• NM_003396.3:c.24C>G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003396.3(WNT9B):​c.24C>G​(p.Ala8Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000087 in 1,149,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 31)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: WNT9B NM_003396.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675

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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP7: Synonymous conserved (PhyloP=0.675 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT9B	NM_003396.3	c.24C>G	p.Ala8Ala	synonymous_variant	Exon 1 of 4	ENST00000290015.7	NP_003387.1
WNT9B	NM_001320458.2	c.24C>G	p.Ala8Ala	synonymous_variant	Exon 1 of 5		NP_001307387.1
LRRC37A2	XM_024450773.2	c.4810-197394C>G		intron_variant	Intron 10 of 10		XP_024306541.1
WNT9B	XM_011525178.3	c.95+18222C>G		intron_variant	Intron 1 of 3		XP_011523480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT9B	ENST00000290015.7	c.24C>G	p.Ala8Ala	synonymous_variant	Exon 1 of 4	1	NM_003396.3	ENSP00000290015.2
WNT9B	ENST00000393461.2	c.24C>G	p.Ala8Ala	synonymous_variant	Exon 1 of 5	2		ENSP00000377105.2
WNT9B	ENST00000575372.5	c.95+18222C>G		intron_variant	Intron 1 of 2	4		ENSP00000458192.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.70e-7 AC: 1 AN: 1149976 Hom.: 0 Cov.: 30 AF XY: 0.00000180 AC XY: 1 AN XY: 557032

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: 0.00000104

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.94

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-44929028;