12-109456223-A-G

Position:

• chr12-109456223-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031954.5(KCTD10):​c.618T>C​(p.Val206=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,613,982 control chromosomes in the GnomAD database, including 24,822 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 0.17 (2240 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22582 hom.)
• Consequence: KCTD10 NM_031954.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

Genes affected

KCTD10 (HGNC:23236): (potassium channel tetramerization domain containing 10) The protein encoded by this gene binds proliferating cell nuclear antigen (PCNA) and may be involved in DNA synthesis and cell proliferation. In addition, the encoded protein may be a tumor suppressor. Several protein-coding and non-protein coding transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.046 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD10	NM_031954.5	c.618T>C	p.Val206=	synonymous_variant	6/7	ENST00000228495.11	NP_114160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD10	ENST00000228495.11	c.618T>C	p.Val206=	synonymous_variant	6/7	1	NM_031954.5	ENSP00000228495	P1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25769 AN: 152056 Hom.: 2244 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.173

GnomAD3 exomes AF: 0.161 AC: 40607 AN: 251486 Hom.: 3360 AF XY: 0.162 AC XY: 21991 AN XY: 135918

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.146

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.174 AC: 254222 AN: 1461806 Hom.: 22582 Cov.: 32 AF XY: 0.172 AC XY: 125332 AN XY: 727216

Gnomad4 AFR exome AF: 0.181

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.169 AC: 25776 AN: 152176 Hom.: 2240 Cov.: 32 AF XY: 0.164 AC XY: 12194 AN XY: 74400

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0989

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.176

Alfa AF: 0.180 Hom.: 3197

Bravo AF: 0.176

Asia WGS AF: 0.150 AC: 521 AN: 3478

EpiCase AF: 0.185

EpiControl AF: 0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.4
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2302706; hg19: chr12-109894028; COSMIC: COSV57326914; COSMIC: COSV57326914;