12-109471206-A-G

Position:

• chr12-109471206-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031954.5(KCTD10):​c.4-1478T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 984,936 control chromosomes in the GnomAD database, including 141,527 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 0.57 (25928 hom., cov: 33)
  • Exomes 𝑓: 0.52 (115599 hom.)
• Consequence: KCTD10 NM_031954.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD10	NM_031954.5	c.4-1478T>C		intron_variant		ENST00000228495.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD10	ENST00000228495.11	c.4-1478T>C		intron_variant		1	NM_031954.5	P1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86958 AN: 151994 Hom.: 25881 Cov.: 33

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.586

GnomAD3 exomes AF: 0.500 AC: 11 AN: 22 Hom.: 4 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.643

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.525 AC: 437194 AN: 832824 Hom.: 115599 Cov.: 29 AF XY: 0.525 AC XY: 201735 AN XY: 384616

Gnomad4 AFR exome AF: 0.741

Gnomad4 AMR exome AF: 0.501

Gnomad4 ASJ exome AF: 0.545

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.412

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.515

GnomAD4 genome AF: 0.572 AC: 87068 AN: 152112 Hom.: 25928 Cov.: 33 AF XY: 0.563 AC XY: 41859 AN XY: 74350

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.586

Alfa AF: 0.522 Hom.: 8628

Bravo AF: 0.586

Asia WGS AF: 0.410 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.92
DANN	Benign	0.34

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: rs2058804; hg19: chr12-109909011; COSMIC: COSV57328279; COSMIC: COSV57328279;