12-121004396-T-A

Variant names:

• chr12-121004396-T-A
• rs3751151
• NM_022895.3:c.546A>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001286191.2(C12orf43):​c.639A>T​(p.Thr213Thr) 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_001286191.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• Publications: 18 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.01).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286191.2. 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
	C12orf43	NM_022895.3	MANE Select	c.546A>T	p.Thr182Thr	synonymous	Exon 6 of 6	NP_075046.1
	C12orf43	NM_001286191.2		c.639A>T	p.Thr213Thr	synonymous	Exon 6 of 6	NP_001273120.1
	C12orf43	NM_001286192.2		c.549A>T	p.Thr183Thr	synonymous	Exon 6 of 6	NP_001273121.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf43	ENST00000288757.7	TSL:1 MANE Select	c.546A>T	p.Thr182Thr	synonymous	Exon 6 of 6	ENSP00000288757.5
	C12orf43	ENST00000537817.5	TSL:1	c.639A>T	p.Thr213Thr	synonymous	Exon 6 of 6	ENSP00000442224.2
	C12orf43	ENST00000886556.1		c.642A>T	p.Thr214Thr	synonymous	Exon 6 of 6	ENSP00000556615.1

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

GnomAD2 exomes AF: 0.270 AC: 67908 AN: 251312 AF XY: 0.268

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 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

African (AFR) AF: 0.301 AC: 10063 AN: 33480

American (AMR) AF: 0.155 AC: 6923 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 6289 AN: 26136

East Asian (EAS) AF: 0.194 AC: 7691 AN: 39698

South Asian (SAS) AF: 0.146 AC: 12625 AN: 86256

European-Finnish (FIN) AF: 0.384 AC: 20439 AN: 53290

Middle Eastern (MID) AF: 0.203 AC: 1172 AN: 5768

European-Non Finnish (NFE) AF: 0.326 AC: 362443 AN: 1111958

Other (OTH) AF: 0.301 AC: 18161 AN: 60392

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

African (AFR) AF: 0.307 AC: 12748 AN: 41496

American (AMR) AF: 0.212 AC: 3244 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3468

East Asian (EAS) AF: 0.246 AC: 1273 AN: 5178

South Asian (SAS) AF: 0.158 AC: 760 AN: 4822

European-Finnish (FIN) AF: 0.374 AC: 3952 AN: 10560

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21931 AN: 67974

Other (OTH) AF: 0.284 AC: 599 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.89
DANN	Benign	0.55
PhyloP100		-0.93
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: rs3751151; hg19: chr12-121442199; COSMIC: COSV56567095; COSMIC: COSV56567095;