12-121000579-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022895.3(C12orf43):c.*3574A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 219,442 control chromosomes in the GnomAD database, including 41,542 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 0.59 (27791 hom., cov: 32)
  • Exomes 𝑓: 0.62 (13751 hom.)
• Consequence: C12orf43 NM_022895.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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]

HNF1A (HGNC:11621): (HNF1 homeobox A) The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C12orf43	NM_022895.3	c.*3574A>G		3_prime_UTR_variant	6/6	ENST00000288757.7
HNF1A	NM_000545.8	c.1769-486T>C		intron_variant		ENST00000257555.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C12orf43	ENST00000288757.7	c.*3574A>G		3_prime_UTR_variant	6/6	1	NM_022895.3	P2
HNF1A	ENST00000257555.11	c.1769-486T>C		intron_variant		1	NM_000545.8	P4

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89722 AN: 151896 Hom.: 27759 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.624 AC: 42049 AN: 67428 Hom.: 13751 Cov.: 0 AF XY: 0.638 AC XY: 22336 AN XY: 34998

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.776

Gnomad4 ASJ exome AF: 0.622

Gnomad4 EAS exome AF: 0.869

Gnomad4 SAS exome AF: 0.751

Gnomad4 FIN exome AF: 0.542

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.597

GnomAD4 genome AF: 0.591 AC: 89797 AN: 152014 Hom.: 27791 Cov.: 32 AF XY: 0.599 AC XY: 44477 AN XY: 74294

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.640

Alfa AF: 0.624 Hom.: 39470

Bravo AF: 0.595

Asia WGS AF: 0.832 AC: 2892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.35
Dann	Benign	0.19

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: rs1169307; hg19: chr12-121438382;