12-48965804-T-G

Variant names:

• chr12-48965804-T-G
• rs3741627
• NM_003394.4:c.*291A>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.*291A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 444,980 control chromosomes in the GnomAD database, including 30,234 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 0.33 (9140 hom., cov: 32)
  • Exomes 𝑓: 0.37 (21094 hom.)
• Consequence: WNT10B NM_003394.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 19 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, Labcorp Genetics (formerly Invitae), Ambry Genetics
• tooth agenesis, selective, 8

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT10B	NM_003394.4	c.*291A>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000301061.9	NP_003385.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT10B	ENST00000301061.9	c.*291A>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_003394.4	ENSP00000301061.4
WNT10B	ENST00000407467.5	c.*743A>C		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000384691.1
WNT10B	ENST00000403957.5	c.*743A>C		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000385980.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49556 AN: 151958 Hom.: 9131 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.367 AC: 107453 AN: 292904 Hom.: 21094 Cov.: 2 AF XY: 0.358 AC XY: 54686 AN XY: 152936

African (AFR) AF: 0.154 AC: 1452 AN: 9404

American (AMR) AF: 0.511 AC: 6930 AN: 13560

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 3958 AN: 9218

East Asian (EAS) AF: 0.467 AC: 8964 AN: 19206

South Asian (SAS) AF: 0.217 AC: 7074 AN: 32614

European-Finnish (FIN) AF: 0.390 AC: 6576 AN: 16850

Middle Eastern (MID) AF: 0.389 AC: 506 AN: 1302

European-Non Finnish (NFE) AF: 0.379 AC: 65783 AN: 173704

Other (OTH) AF: 0.364 AC: 6210 AN: 17046

GnomAD4 genome AF: 0.326 AC: 49576 AN: 152076 Hom.: 9140 Cov.: 32 AF XY: 0.330 AC XY: 24504 AN XY: 74338

African (AFR) AF: 0.156 AC: 6491 AN: 41500

American (AMR) AF: 0.476 AC: 7269 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2403 AN: 5166

South Asian (SAS) AF: 0.220 AC: 1057 AN: 4814

European-Finnish (FIN) AF: 0.376 AC: 3976 AN: 10580

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25596 AN: 67960

Other (OTH) AF: 0.360 AC: 760 AN: 2112

Alfa AF: 0.370 Hom.: 17212

Bravo AF: 0.337

Asia WGS AF: 0.363 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		-0.068
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: rs3741627; hg19: chr12-49359587;