rs833834

Variant names:

• chr12-48968996-T-A
• rs833834
• NM_003394.4:c.338-677A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-48968996-T-A
• chr12-48968996-T-C
• chr12-48968996-T-G

Variant summary

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

The NM_003394.4(WNT10B):​c.338-677A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000033 in 302,682 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: 30)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: WNT10B NM_003394.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 5 publications found

Genes affected

WNT10B (HGNC:12775): (Wnt family member 10B) 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 may be involved in breast cancer, and its protein signaling is likely a molecular switch that governs adipogenesis. This protein is 96% identical to the mouse Wnt10b protein at the amino acid level. This gene is clustered with another family member, WNT1, in the chromosome 12q13 region. [provided by RefSeq, Jul 2008]

WNT10B Gene-Disease associations (from GenCC):

• split hand-foot malformation 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• tooth agenesis, selective, 8

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• split hand-foot malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003394.4. 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
	WNT10B	NM_003394.4	MANE Select	c.338-677A>T		intron	N/A	NP_003385.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT10B	ENST00000301061.9	TSL:1 MANE Select	c.338-677A>T		intron	N/A	ENSP00000301061.4	O00744-1
	WNT10B	ENST00000407467.5	TSL:2	c.338-677A>T		intron	N/A	ENSP00000384691.1	O00744-2
	WNT10B	ENST00000403957.5	TSL:5	c.338-677A>T		intron	N/A	ENSP00000385980.1	B5MCC8

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000330 AC: 1 AN: 302682 Hom.: 0 AF XY: 0.00000585 AC XY: 1 AN XY: 170826

African (AFR) AF: 0.00 AC: 0 AN: 8078

American (AMR) AF: 0.00 AC: 0 AN: 25472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9598

East Asian (EAS) AF: 0.00 AC: 0 AN: 9072

South Asian (SAS) AF: 0.0000176 AC: 1 AN: 56732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 151214

Other (OTH) AF: 0.00 AC: 0 AN: 13586

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 4824

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.2
DANN	Benign	0.78
PhyloP100		-1.2

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: rs833834; hg19: chr12-49362779;