rs694997

Variant names:

• chr13-76885933-C-T
• rs694997
• NM_138444.4:c.216G>A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_138444.4(KCTD12):​c.216G>A​(p.Leu72Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,593,870 control chromosomes in the GnomAD database, including 40 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 0.0079 (17 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (23 hom.)
• Consequence: KCTD12 NM_138444.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56

Genes affected

KCTD12 (HGNC:14678): (potassium channel tetramerization domain containing 12) Enables identical protein binding activity. Predicted to be involved in protein homooligomerization. Predicted to act upstream of or within regulation of G protein-coupled receptor signaling pathway. Predicted to be located in cell projection. Predicted to be part of receptor complex. Predicted to be active in postsynaptic membrane and presynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=3.56 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00789 (1202/152358) while in subpopulation AFR AF= 0.0265 (1104/41584). AF 95% confidence interval is 0.0252. There are 17 homozygotes in gnomad4. There are 592 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD12	NM_138444.4	c.216G>A	p.Leu72Leu	synonymous_variant	Exon 1 of 1	ENST00000377474.4	NP_612453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD12	ENST00000377474.4	c.216G>A	p.Leu72Leu	synonymous_variant	Exon 1 of 1	6	NM_138444.4	ENSP00000366694.2

Frequencies

GnomAD3 genomes AF: 0.00787 AC: 1198 AN: 152240 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00264 AC: 578 AN: 218790 Hom.: 5 AF XY: 0.00207 AC XY: 252 AN XY: 121498

Gnomad AFR exome AF: 0.0270

Gnomad AMR exome AF: 0.00407

Gnomad ASJ exome AF: 0.000950

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000342

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000432

Gnomad OTH exome AF: 0.00470

GnomAD4 exome AF: 0.00114 AC: 1647 AN: 1441512 Hom.: 23 Cov.: 31 AF XY: 0.00102 AC XY: 730 AN XY: 717402

Gnomad4 AFR exome AF: 0.0281

Gnomad4 AMR exome AF: 0.00405

Gnomad4 ASJ exome AF: 0.000577

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000821

Gnomad4 FIN exome AF: 0.0000522

Gnomad4 NFE exome AF: 0.000333

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.00789 AC: 1202 AN: 152358 Hom.: 17 Cov.: 33 AF XY: 0.00795 AC XY: 592 AN XY: 74504

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.00372

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00442 Hom.: 1

Bravo AF: 0.00925

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Uncertain	0.98

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: rs694997; hg19: chr13-77460068;