chr12-121003658-G-T

Variant names:

• chr12-121003658-G-T
• rs1169312
• NM_022895.3:c.*495C>A

Variant summary

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

The NM_022895.3(C12orf43):​c.*495C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 155,066 control chromosomes in the GnomAD database, including 8,966 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 (8738 hom., cov: 32)
  • Exomes 𝑓: 0.35 (228 hom.)
• Consequence: C12orf43 NM_022895.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 17 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=-0.85).
• 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.*495C>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000288757.7	NP_075046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf43	ENST00000288757.7	c.*495C>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_022895.3	ENSP00000288757.5

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48532 AN: 151934 Hom.: 8736 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.352 AC: 1062 AN: 3014 Hom.: 228 Cov.: 0 AF XY: 0.376 AC XY: 584 AN XY: 1552

African (AFR) AF: 0.0714 AC: 3 AN: 42

American (AMR) AF: 0.371 AC: 152 AN: 410

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 30 AN: 60

East Asian (EAS) AF: 0.538 AC: 42 AN: 78

South Asian (SAS) AF: 0.505 AC: 111 AN: 220

European-Finnish (FIN) AF: 0.386 AC: 27 AN: 70

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.327 AC: 650 AN: 1986

Other (OTH) AF: 0.331 AC: 47 AN: 142

GnomAD4 genome AF: 0.319 AC: 48532 AN: 152052 Hom.: 8738 Cov.: 32 AF XY: 0.328 AC XY: 24386 AN XY: 74294

African (AFR) AF: 0.145 AC: 6009 AN: 41520

American (AMR) AF: 0.394 AC: 6018 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2523 AN: 5144

South Asian (SAS) AF: 0.513 AC: 2476 AN: 4826

European-Finnish (FIN) AF: 0.384 AC: 4053 AN: 10556

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24326 AN: 67960

Other (OTH) AF: 0.375 AC: 791 AN: 2108

Alfa AF: 0.342 Hom.: 21825

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	-0.85
CADD	Benign	0.76
DANN	Benign	0.40
PhyloP100		-0.59
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: rs1169312; hg19: chr12-121441461;