12-121004867-T-C

Variant names:

• chr12-121004867-T-C
• rs1169313
• NM_022895.3:c.452+136A>G

Variant summary

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

The NM_022895.3(C12orf43):​c.452+136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 600,270 control chromosomes in the GnomAD database, including 42,156 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 0.32 (8761 hom., cov: 31)
  • Exomes 𝑓: 0.38 (33395 hom.)
• Consequence: C12orf43 NM_022895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 46 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf43	NM_022895.3	c.452+136A>G		intron_variant	Intron 5 of 5	ENST00000288757.7	NP_075046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf43	ENST00000288757.7	c.452+136A>G		intron_variant	Intron 5 of 5	1	NM_022895.3	ENSP00000288757.5

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48590 AN: 151878 Hom.: 8759 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.377 AC: 169116 AN: 448274 Hom.: 33395 AF XY: 0.381 AC XY: 86111 AN XY: 226228

African (AFR) AF: 0.140 AC: 1488 AN: 10634

American (AMR) AF: 0.405 AC: 4543 AN: 11228

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 5914 AN: 11300

East Asian (EAS) AF: 0.536 AC: 13838 AN: 25796

South Asian (SAS) AF: 0.509 AC: 9966 AN: 19564

European-Finnish (FIN) AF: 0.363 AC: 13682 AN: 37686

Middle Eastern (MID) AF: 0.546 AC: 973 AN: 1782

European-Non Finnish (NFE) AF: 0.358 AC: 109752 AN: 306558

Other (OTH) AF: 0.378 AC: 8960 AN: 23726

GnomAD4 genome AF: 0.320 AC: 48590 AN: 151996 Hom.: 8761 Cov.: 31 AF XY: 0.329 AC XY: 24415 AN XY: 74268

African (AFR) AF: 0.145 AC: 6021 AN: 41480

American (AMR) AF: 0.394 AC: 6023 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1811 AN: 3466

East Asian (EAS) AF: 0.490 AC: 2526 AN: 5160

South Asian (SAS) AF: 0.513 AC: 2465 AN: 4806

European-Finnish (FIN) AF: 0.384 AC: 4056 AN: 10556

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.359 AC: 24369 AN: 67942

Other (OTH) AF: 0.377 AC: 795 AN: 2110

Alfa AF: 0.348 Hom.: 12884

Bravo AF: 0.311

Asia WGS AF: 0.478 AC: 1660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.43
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1169313; hg19: chr12-121442670; COSMIC: COSV56567048; COSMIC: COSV56567048;