rs41287030

Positions:

• chr13-76885086-G-A
• chr13-76885086-G-C
• chr13-76885086-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_138444.4(KCTD12):​c.*85C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,481,002 control chromosomes in the GnomAD database, including 202 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 0.011 (14 hom., cov: 32)
  • Exomes 𝑓: 0.013 (188 hom.)
• Consequence: KCTD12 NM_138444.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.011 (1680/152202) while in subpopulation SAS AF= 0.0293 (141/4812). AF 95% confidence interval is 0.0254. There are 14 homozygotes in gnomad4. There are 853 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD12	NM_138444.4	c.*85C>T		3_prime_UTR_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.*85C>T		3_prime_UTR_variant	1/1		NM_138444.4	ENSP00000366694	P1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1678 AN: 152084 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00656

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0235

GnomAD4 exome AF: 0.0134 AC: 17829 AN: 1328800 Hom.: 188 Cov.: 22 AF XY: 0.0140 AC XY: 9135 AN XY: 654464

Gnomad4 AFR exome AF: 0.00358

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.0148

Gnomad4 EAS exome AF: 0.00257

Gnomad4 SAS exome AF: 0.0297

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.0157

GnomAD4 genome AF: 0.0110 AC: 1680 AN: 152202 Hom.: 14 Cov.: 32 AF XY: 0.0115 AC XY: 853 AN XY: 74420

Gnomad4 AFR AF: 0.00349

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00658

Gnomad4 SAS AF: 0.0293

Gnomad4 FIN AF: 0.0108

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00591 Hom.: 1

Bravo AF: 0.0109

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.72

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: rs41287030; hg19: chr13-77459221;