rs56209061

chr12-109467880-G-A

Variant summary

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

The NM_031954.5(KCTD10):c.217+1635C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 152,190 control chromosomes in the GnomAD database, including 266 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 0.047 (266 hom., cov: 31)
• Consequence: KCTD10 NM_031954.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD10	NM_031954.5	c.217+1635C>T		intron_variant		ENST00000228495.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD10	ENST00000228495.11	c.217+1635C>T		intron_variant		1	NM_031954.5	P1

Frequencies

GnomAD3 genomes AF: 0.0472 AC: 7179 AN: 152072 Hom.: 266 Cov.: 31

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0661

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0471 AC: 7175 AN: 152190 Hom.: 266 Cov.: 31 AF XY: 0.0465 AC XY: 3462 AN XY: 74410

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.0620

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.0462

Gnomad4 NFE AF: 0.0657

Gnomad4 OTH AF: 0.0654

Alfa AF: 0.0612 Hom.: 71

Bravo AF: 0.0476

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.7
Dann	Benign	0.63

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: rs56209061; hg19: chr12-109905685;