chr12-48966206-G-A

Variant names:

• chr12-48966206-G-A
• rs1051886
• NM_003394.4:c.1059C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003394.4(WNT10B):​c.1059C>T​(p.His353His) variant causes a synonymous change. The variant allele was found at a frequency of 0.37 in 1,613,570 control chromosomes in the GnomAD database, including 115,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9136 hom., cov: 33)
  • Exomes 𝑓: 0.37 (106074 hom.)
• Consequence: WNT10B NM_003394.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 5.64
• Publications: 32 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 12-48966206-G-A is Benign according to our data. Variant chr12-48966206-G-A is described in ClinVar as Benign. ClinVar VariationId is 1175136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.466 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.1059C>T	p.His353His	synonymous	Exon 5 of 5	NP_003385.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT10B	ENST00000301061.9	TSL:1 MANE Select	c.1059C>T	p.His353His	synonymous	Exon 5 of 5	ENSP00000301061.4	O00744-1
	WNT10B	ENST00000407467.5	TSL:2	c.*341C>T		3_prime_UTR	Exon 6 of 6	ENSP00000384691.1	O00744-2
	WNT10B	ENST00000403957.5	TSL:5	c.*341C>T		3_prime_UTR	Exon 6 of 6	ENSP00000385980.1	B5MCC8

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49537 AN: 152070 Hom.: 9126 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.382 AC: 95727 AN: 250614 AF XY: 0.373

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.552

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.465

Gnomad FIN exome AF: 0.385

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.389

GnomAD4 exome AF: 0.375 AC: 547613 AN: 1461380 Hom.: 106074 Cov.: 70 AF XY: 0.371 AC XY: 269867 AN XY: 726966

African (AFR) AF: 0.150 AC: 5012 AN: 33478

American (AMR) AF: 0.538 AC: 24049 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 11348 AN: 26136

East Asian (EAS) AF: 0.475 AC: 18841 AN: 39696

South Asian (SAS) AF: 0.224 AC: 19283 AN: 86248

European-Finnish (FIN) AF: 0.389 AC: 20657 AN: 53142

Middle Eastern (MID) AF: 0.380 AC: 2191 AN: 5768

European-Non Finnish (NFE) AF: 0.381 AC: 424156 AN: 1111830

Other (OTH) AF: 0.366 AC: 22076 AN: 60384

GnomAD4 genome AF: 0.326 AC: 49558 AN: 152190 Hom.: 9136 Cov.: 33 AF XY: 0.329 AC XY: 24500 AN XY: 74412

African (AFR) AF: 0.156 AC: 6469 AN: 41536

American (AMR) AF: 0.476 AC: 7272 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3472

East Asian (EAS) AF: 0.466 AC: 2411 AN: 5174

South Asian (SAS) AF: 0.219 AC: 1060 AN: 4832

European-Finnish (FIN) AF: 0.376 AC: 3979 AN: 10596

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

European-Non Finnish (NFE) AF: 0.376 AC: 25586 AN: 67974

Other (OTH) AF: 0.360 AC: 761 AN: 2114

Alfa AF: 0.374 Hom.: 19685

Bravo AF: 0.336

Asia WGS AF: 0.363 AC: 1261 AN: 3478

EpiCase AF: 0.389

EpiControl AF: 0.393

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Split hand-foot malformation 6 (1)
-	-	1	Tooth agenesis, selective, 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.6
DANN	Benign	0.62
PhyloP100		5.6
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: rs1051886; hg19: chr12-49359989; COSMIC: COSV56405412; COSMIC: COSV56405412;