NM_003394.4:c.338-677A>C

Variant names:

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

Variant summary

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

The NM_003394.4(WNT10B):​c.338-677A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 454,650 control chromosomes in the GnomAD database, including 203,289 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 0.90 (62213 hom., cov: 30)
  • Exomes 𝑓: 0.96 (141076 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

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>C		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>C		intron	N/A	ENSP00000301061.4	O00744-1
	WNT10B	ENST00000407467.5	TSL:2	c.338-677A>C		intron	N/A	ENSP00000384691.1	O00744-2
	WNT10B	ENST00000403957.5	TSL:5	c.338-677A>C		intron	N/A	ENSP00000385980.1	B5MCC8

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136221 AN: 151896 Hom.: 62194 Cov.: 30

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.903

GnomAD4 exome AF: 0.964 AC: 291833 AN: 302636 Hom.: 141076 AF XY: 0.966 AC XY: 164949 AN XY: 170794

African (AFR) AF: 0.694 AC: 5601 AN: 8066

American (AMR) AF: 0.967 AC: 24628 AN: 25472

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 9249 AN: 9594

East Asian (EAS) AF: 1.00 AC: 9072 AN: 9072

South Asian (SAS) AF: 0.966 AC: 54808 AN: 56726

European-Finnish (FIN) AF: 0.994 AC: 26296 AN: 26468

Middle Eastern (MID) AF: 0.909 AC: 2237 AN: 2460

European-Non Finnish (NFE) AF: 0.972 AC: 146944 AN: 151192

Other (OTH) AF: 0.957 AC: 12998 AN: 13586

GnomAD4 genome AF: 0.897 AC: 136284 AN: 152014 Hom.: 62213 Cov.: 30 AF XY: 0.900 AC XY: 66861 AN XY: 74310

African (AFR) AF: 0.702 AC: 29072 AN: 41396

American (AMR) AF: 0.941 AC: 14377 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3343 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5158 AN: 5162

South Asian (SAS) AF: 0.972 AC: 4685 AN: 4818

European-Finnish (FIN) AF: 0.994 AC: 10529 AN: 10596

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66048 AN: 67976

Other (OTH) AF: 0.904 AC: 1908 AN: 2110

Alfa AF: 0.904 Hom.: 4824

Bravo AF: 0.884

Asia WGS AF: 0.973 AC: 3382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.5
DANN	Benign	0.79
PhyloP100		-1.2
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: rs833834; hg19: chr12-49362779;