13-73691425-T-C

Position:

• chr13-73691425-T-C

Variant summary

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

The ENST00000703967(KLF12):​c.*4065A>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 0.626 in 152,528 control chromosomes in the GnomAD database, including 31,928 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 0.63 (31808 hom., cov: 33)
  • Exomes 𝑓: 0.75 (120 hom.)
• Consequence: KLF12 ENST00000703967 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

Genes affected

KLF12 (HGNC:6346): (KLF transcription factor 12) Activator protein-2 alpha (AP-2 alpha) is a developmentally-regulated transcription factor and important regulator of gene expression during vertebrate development and carcinogenesis. The protein encoded by this gene is a member of the Kruppel-like zinc finger protein family and can repress expression of the AP-2 alpha gene by binding to a specific site in the AP-2 alpha gene promoter. Repression by the encoded protein requires binding with a corepressor, CtBP1. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF12	NM_001400136.1	c.*4065A>G		3_prime_UTR_variant	8/8		NP_001387065.1
KLF12	NM_001400139.1	c.*4065A>G		3_prime_UTR_variant	8/8		NP_001387068.1
KLF12	NM_001400141.1	c.*4065A>G		3_prime_UTR_variant	8/8		NP_001387070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF12	ENST00000377669	c.*4065A>G		3_prime_UTR_variant	8/8	1		ENSP00000366897.2
KLF12	ENST00000703967	c.*4065A>G		3_prime_UTR_variant	8/8			ENSP00000515592.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95144 AN: 151982 Hom.: 31813 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.656

GnomAD4 exome AF: 0.750 AC: 321 AN: 428 Hom.: 120 Cov.: 0 AF XY: 0.723 AC XY: 188 AN XY: 260

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.626 AC: 95162 AN: 152100 Hom.: 31808 Cov.: 33 AF XY: 0.627 AC XY: 46590 AN XY: 74354

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.651

Alfa AF: 0.713 Hom.: 38741

Bravo AF: 0.618

Asia WGS AF: 0.606 AC: 2105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.56

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: rs7993625; hg19: chr13-74265562;