12-121016510-C-A

Variant names:

• chr12-121016510-C-A
• rs2258287
• NM_022895.3:c.-36G>T

Variant summary

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

The NM_022895.3(C12orf43):​c.-36G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,611,520 control chromosomes in the GnomAD database, including 102,540 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 0.35 (9698 hom., cov: 34)
  • Exomes 𝑓: 0.35 (92842 hom.)
• Consequence: C12orf43 NM_022895.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 33 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf43	NM_022895.3	c.-36G>T		upstream_gene_variant		ENST00000288757.7	NP_075046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf43	ENST00000288757.7	c.-36G>T		upstream_gene_variant		1	NM_022895.3	ENSP00000288757.5

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52540 AN: 152036 Hom.: 9688 Cov.: 34

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.361

GnomAD2 exomes AF: 0.395 AC: 98558 AN: 249496 AF XY: 0.399

Gnomad AFR exome AF: 0.292

Gnomad AMR exome AF: 0.390

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.738

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.380

GnomAD4 exome AF: 0.347 AC: 506015 AN: 1459366 Hom.: 92842 Cov.: 42 AF XY: 0.352 AC XY: 255134 AN XY: 725774

African (AFR) AF: 0.287 AC: 9580 AN: 33432

American (AMR) AF: 0.391 AC: 17477 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 12475 AN: 26110

East Asian (EAS) AF: 0.720 AC: 28547 AN: 39670

South Asian (SAS) AF: 0.491 AC: 42303 AN: 86212

European-Finnish (FIN) AF: 0.325 AC: 17122 AN: 52676

Middle Eastern (MID) AF: 0.512 AC: 2953 AN: 5766

European-Non Finnish (NFE) AF: 0.318 AC: 352842 AN: 1110508

Other (OTH) AF: 0.377 AC: 22716 AN: 60332

GnomAD4 genome AF: 0.346 AC: 52581 AN: 152154 Hom.: 9698 Cov.: 34 AF XY: 0.354 AC XY: 26343 AN XY: 74370

African (AFR) AF: 0.294 AC: 12219 AN: 41508

American (AMR) AF: 0.376 AC: 5755 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1633 AN: 3464

East Asian (EAS) AF: 0.734 AC: 3794 AN: 5170

South Asian (SAS) AF: 0.499 AC: 2407 AN: 4822

European-Finnish (FIN) AF: 0.333 AC: 3524 AN: 10580

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21867 AN: 68002

Other (OTH) AF: 0.366 AC: 774 AN: 2112

Alfa AF: 0.309 Hom.: 3518

Bravo AF: 0.347

Asia WGS AF: 0.615 AC: 2133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.7
DANN	Benign	0.67
PhyloP100		-0.22
PromoterAI		-0.025	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2258287; hg19: chr12-121454313; COSMIC: COSV105855574;