rs3121310

Positions:

• chr1-228037123-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000284523.2(WNT3A):​c.314-13533A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 151,936 control chromosomes in the GnomAD database, including 29,753 homozygotes. 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: 𝑓 0.62 (29753 hom., cov: 32)
• Consequence: WNT3A ENST00000284523.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.24

Genes affected

WNT3A (HGNC:15983): (Wnt family member 3A) The WNT gene family consists of structurally related genes which 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. It encodes a protein which shows 96% amino acid identity to mouse Wnt3A protein, and 84% to human WNT3 protein, another WNT gene product. This gene is clustered with WNT14 gene, another family member, in chromosome 1q42 region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT3A	NM_033131.4	c.314-13533A>G		intron_variant		ENST00000284523.2	NP_149122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT3A	ENST00000284523.2	c.314-13533A>G		intron_variant		1	NM_033131.4	ENSP00000284523	P1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 93980 AN: 151818 Hom.: 29748 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.638

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.619 AC: 94016 AN: 151936 Hom.: 29753 Cov.: 32 AF XY: 0.627 AC XY: 46534 AN XY: 74274

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.640

Alfa AF: 0.663 Hom.: 44168

Bravo AF: 0.602

Asia WGS AF: 0.715 AC: 2490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.021
DANN	Benign	0.14

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: rs3121310; hg19: chr1-228224824; COSMIC: COSV52729927;