rs3751151

Positions:

• chr12-121004396-T-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_022895.3(C12orf43):​c.546A>T​(p.Thr182Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,613,802 control chromosomes in the GnomAD database, including 77,533 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 0.30 (7005 hom., cov: 32)
  • Exomes 𝑓: 0.30 (70528 hom.)
• Consequence: C12orf43 NM_022895.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929

Genes affected

C12orf43 (HGNC:25719): (chromosome 12 open reading frame 43) Predicted to be involved in Spemann organizer formation and negative regulation of Wnt signaling pathway. Predicted to be located in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

C12orf43 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.929 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C12orf43	NM_022895.3	c.546A>T	p.Thr182Thr	synonymous_variant	6/6	ENST00000288757.7	NP_075046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C12orf43	ENST00000288757.7	c.546A>T	p.Thr182Thr	synonymous_variant	6/6	1	NM_022895.3	ENSP00000288757.5

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45603 AN: 151982 Hom.: 6996 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.288

GnomAD3 exomes AF: 0.270 AC: 67908 AN: 251312 Hom.: 10054 AF XY: 0.268 AC XY: 36451 AN XY: 135844

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.248

Gnomad SAS exome AF: 0.144

Gnomad FIN exome AF: 0.375

Gnomad NFE exome AF: 0.322

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.305 AC: 445806 AN: 1461700 Hom.: 70528 Cov.: 43 AF XY: 0.300 AC XY: 218362 AN XY: 727164

Gnomad4 AFR exome AF: 0.301

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.300 AC: 45642 AN: 152102 Hom.: 7005 Cov.: 32 AF XY: 0.296 AC XY: 21999 AN XY: 74330

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.284

Alfa AF: 0.309 Hom.: 2419

Bravo AF: 0.290

Asia WGS AF: 0.238 AC: 828 AN: 3478

EpiCase AF: 0.311

EpiControl AF: 0.312

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.89
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs3751151; hg19: chr12-121442199; COSMIC: COSV56567095; COSMIC: COSV56567095;