rs3121310

Variant names:

• chr1-228037123-A-G
• rs3121310
• NM_033131.4:c.314-13533A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033131.4(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 NM_033131.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.24
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
WNT3A	NM_033131.4	c.314-13533A>G		intron_variant	Intron 2 of 3	ENST00000284523.2	NP_149122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT3A	ENST00000284523.2	c.314-13533A>G		intron_variant	Intron 2 of 3	1	NM_033131.4	ENSP00000284523.1

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

African (AFR) AF: 0.465 AC: 19274 AN: 41442

American (AMR) AF: 0.649 AC: 9921 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2230 AN: 3472

East Asian (EAS) AF: 0.657 AC: 3364 AN: 5120

South Asian (SAS) AF: 0.740 AC: 3572 AN: 4824

European-Finnish (FIN) AF: 0.747 AC: 7905 AN: 10588

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45539 AN: 67878

Other (OTH) AF: 0.640 AC: 1351 AN: 2112

Alfa AF: 0.657 Hom.: 55008

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
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism (auto)

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