chr12-109467880-G-A

Variant names:

• chr12-109467880-G-A
• rs56209061
• NM_031954.5:c.217+1635C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001317395.2(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_001317395.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 2 publications found

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]

KCTD10 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317395.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD10	NM_031954.5	MANE Select	c.217+1635C>T		intron	N/A	NP_114160.1
	KCTD10	NM_001317395.2		c.217+1635C>T		intron	N/A	NP_001304324.1
	KCTD10	NM_001317399.2		c.217+1635C>T		intron	N/A	NP_001304328.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD10	ENST00000228495.11	TSL:1 MANE Select	c.217+1635C>T		intron	N/A	ENSP00000228495.6
	KCTD10	ENST00000540411.5	TSL:1	c.208+1635C>T		intron	N/A	ENSP00000441672.1
	KCTD10	ENST00000948235.1		c.217+1635C>T		intron	N/A	ENSP00000618294.1

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

African (AFR) AF: 0.0111 AC: 460 AN: 41518

American (AMR) AF: 0.0620 AC: 948 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.0243 AC: 117 AN: 4824

European-Finnish (FIN) AF: 0.0462 AC: 490 AN: 10598

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0657 AC: 4466 AN: 68006

Other (OTH) AF: 0.0654 AC: 138 AN: 2110

Alfa AF: 0.0603 Hom.: 71

Bravo AF: 0.0476

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		-0.29
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56209061; hg19: chr12-109905685;