13-73764967-G-T

Variant names:

• chr13-73764967-G-T
• rs3764134
• NM_001400136.1:c.840C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001400136.1(KLF12):​c.840C>A​(p.Gly280Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,550,362 control chromosomes in the GnomAD database, including 225,591 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 0.48 (18278 hom., cov: 31)
  • Exomes 𝑓: 0.53 (207313 hom.)
• Consequence: KLF12 NM_001400136.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.333 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400136.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF12	NM_001400136.1	MANE Select	c.840C>A	p.Gly280Gly	synonymous	Exon 6 of 8	NP_001387065.1
	KLF12	NM_001400139.1		c.840C>A	p.Gly280Gly	synonymous	Exon 6 of 8	NP_001387068.1
	KLF12	NM_001400141.1		c.840C>A	p.Gly280Gly	synonymous	Exon 6 of 8	NP_001387070.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF12	ENST00000703967.1	MANE Select	c.840C>A	p.Gly280Gly	synonymous	Exon 6 of 8	ENSP00000515592.1
	KLF12	ENST00000377669.7	TSL:1	c.840C>A	p.Gly280Gly	synonymous	Exon 6 of 8	ENSP00000366897.2

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72964 AN: 151756 Hom.: 18268 Cov.: 31

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.500

GnomAD2 exomes AF: 0.483 AC: 118530 AN: 245636 AF XY: 0.497

Gnomad AFR exome AF: 0.391

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.616

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.552

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.535 AC: 748115 AN: 1398488 Hom.: 207313 Cov.: 28 AF XY: 0.538 AC XY: 376289 AN XY: 699048

African (AFR) AF: 0.382 AC: 12336 AN: 32326

American (AMR) AF: 0.360 AC: 15857 AN: 44032

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 15493 AN: 25520

East Asian (EAS) AF: 0.194 AC: 7656 AN: 39514

South Asian (SAS) AF: 0.582 AC: 49011 AN: 84152

European-Finnish (FIN) AF: 0.444 AC: 23617 AN: 53166

Middle Eastern (MID) AF: 0.554 AC: 3127 AN: 5640

European-Non Finnish (NFE) AF: 0.559 AC: 590199 AN: 1055928

Other (OTH) AF: 0.529 AC: 30819 AN: 58210

GnomAD4 genome AF: 0.481 AC: 73005 AN: 151874 Hom.: 18278 Cov.: 31 AF XY: 0.475 AC XY: 35264 AN XY: 74186

African (AFR) AF: 0.402 AC: 16621 AN: 41376

American (AMR) AF: 0.406 AC: 6192 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2125 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1020 AN: 5152

South Asian (SAS) AF: 0.570 AC: 2740 AN: 4808

European-Finnish (FIN) AF: 0.439 AC: 4619 AN: 10526

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37809 AN: 67970

Other (OTH) AF: 0.494 AC: 1043 AN: 2112

Alfa AF: 0.525 Hom.: 41690

Bravo AF: 0.473

Asia WGS AF: 0.384 AC: 1332 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.4
DANN	Benign	0.71
PhyloP100		0.33
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: rs3764134; hg19: chr13-74339104; COSMIC: COSV66569729;