rs34544607

Positions:

• chr13-76885615-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_138444.4(KCTD12):​c.534G>C​(p.Thr178Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 1,504,778 control chromosomes in the GnomAD database, including 1,442 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 0.039 (130 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1312 hom.)
• Consequence: KCTD12 NM_138444.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD12	NM_138444.4	c.534G>C	p.Thr178Thr	synonymous_variant	1/1	ENST00000377474.4	NP_612453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD12	ENST00000377474.4	c.534G>C	p.Thr178Thr	synonymous_variant	1/1	6	NM_138444.4	ENSP00000366694.2

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5913 AN: 152126 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0371

Gnomad OTH AF: 0.0425

GnomAD3 exomes AF: 0.0475 AC: 4912 AN: 103406 Hom.: 164 AF XY: 0.0511 AC XY: 2943 AN XY: 57568

Gnomad AFR exome AF: 0.0578

Gnomad AMR exome AF: 0.0205

Gnomad ASJ exome AF: 0.0886

Gnomad EAS exome AF: 0.000234

Gnomad SAS exome AF: 0.101

Gnomad FIN exome AF: 0.0371

Gnomad NFE exome AF: 0.0443

Gnomad OTH exome AF: 0.0482

GnomAD4 exome AF: 0.0406 AC: 54894 AN: 1352544 Hom.: 1312 Cov.: 31 AF XY: 0.0418 AC XY: 27897 AN XY: 666812

Gnomad4 AFR exome AF: 0.0444

Gnomad4 AMR exome AF: 0.0204

Gnomad4 ASJ exome AF: 0.0782

Gnomad4 EAS exome AF: 0.000114

Gnomad4 SAS exome AF: 0.0900

Gnomad4 FIN exome AF: 0.0292

Gnomad4 NFE exome AF: 0.0384

Gnomad4 OTH exome AF: 0.0423

GnomAD4 genome AF: 0.0388 AC: 5913 AN: 152234 Hom.: 130 Cov.: 32 AF XY: 0.0393 AC XY: 2925 AN XY: 74420

Gnomad4 AFR AF: 0.0423

Gnomad4 AMR AF: 0.0267

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.000583

Gnomad4 SAS AF: 0.0907

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0370

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0419 Hom.: 29

Bravo AF: 0.0378

Asia WGS AF: 0.0370 AC: 127 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.88

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: rs34544607; hg19: chr13-77459750;