12-109471709-G-C

Variant names:

• chr12-109471709-G-C
• rs10850219
• NM_031954.5:c.4-1981C>G

Variant summary

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

The ENST00000228495.11(KCTD10):​c.4-1981C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,078 control chromosomes in the GnomAD database, including 2,990 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 0.19 (2990 hom., cov: 32)
• Consequence: KCTD10 ENST00000228495.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000228495.11. 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.4-1981C>G		intron	N/A	NP_114160.1
	KCTD10	NM_001317395.2		c.4-1981C>G		intron	N/A	NP_001304324.1
	KCTD10	NM_001317399.2		c.4-1981C>G		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.4-1981C>G		intron	N/A	ENSP00000228495.6
	KCTD10	ENST00000542858.1	TSL:3	c.4-1981C>G		intron	N/A	ENSP00000445129.1
	KCTD10	ENST00000542262.5	TSL:4	c.4-1981C>G		intron	N/A	ENSP00000437348.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29001 AN: 151960 Hom.: 2984 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0321

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.191 AC: 29030 AN: 152078 Hom.: 2990 Cov.: 32 AF XY: 0.189 AC XY: 14054 AN XY: 74348

African (AFR) AF: 0.173 AC: 7159 AN: 41474

American (AMR) AF: 0.176 AC: 2691 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3466

East Asian (EAS) AF: 0.0320 AC: 166 AN: 5186

South Asian (SAS) AF: 0.167 AC: 805 AN: 4814

European-Finnish (FIN) AF: 0.206 AC: 2181 AN: 10570

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14361 AN: 67986

Other (OTH) AF: 0.219 AC: 460 AN: 2104

Alfa AF: 0.117 Hom.: 243

Bravo AF: 0.189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.19
PhyloP100		0.19
Mutation Taster		=100/0	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: rs10850219; hg19: chr12-109909514; COSMIC: COSV57327314; COSMIC: COSV57327314;