rs2338104

Variant names:

• chr12-109457363-C-G
• rs2338104
• ENST00000545759.5:n.2267G>C

Variant summary

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

The ENST00000545759.5(KCTD10):​n.2267G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 341,572 control chromosomes in the GnomAD database, including 52,920 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 (25961 hom., cov: 33)
  • Exomes 𝑓: 0.52 (26959 hom.)
• Consequence: KCTD10 ENST00000545759.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• Publications: 96 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD10	NM_031954.5	c.527+267G>C		intron_variant	Intron 5 of 6	ENST00000228495.11	NP_114160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD10	ENST00000228495.11	c.527+267G>C		intron_variant	Intron 5 of 6	1	NM_031954.5	ENSP00000228495.6

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87038 AN: 151930 Hom.: 25915 Cov.: 33

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.523 AC: 99179 AN: 189524 Hom.: 26959 Cov.: 2 AF XY: 0.521 AC XY: 50813 AN XY: 97504

African (AFR) AF: 0.748 AC: 4295 AN: 5744

American (AMR) AF: 0.513 AC: 3511 AN: 6846

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 3655 AN: 6678

East Asian (EAS) AF: 0.324 AC: 4976 AN: 15336

South Asian (SAS) AF: 0.453 AC: 4475 AN: 9886

European-Finnish (FIN) AF: 0.473 AC: 6131 AN: 12964

Middle Eastern (MID) AF: 0.596 AC: 570 AN: 956

European-Non Finnish (NFE) AF: 0.547 AC: 65117 AN: 119126

Other (OTH) AF: 0.538 AC: 6449 AN: 11988

GnomAD4 genome AF: 0.573 AC: 87145 AN: 152048 Hom.: 25961 Cov.: 33 AF XY: 0.564 AC XY: 41917 AN XY: 74360

African (AFR) AF: 0.734 AC: 30461 AN: 41488

American (AMR) AF: 0.504 AC: 7700 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1852 AN: 3470

East Asian (EAS) AF: 0.360 AC: 1866 AN: 5180

South Asian (SAS) AF: 0.406 AC: 1957 AN: 4822

European-Finnish (FIN) AF: 0.465 AC: 4900 AN: 10548

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36476 AN: 67966

Other (OTH) AF: 0.588 AC: 1236 AN: 2102

Alfa AF: 0.542 Hom.: 12607

Bravo AF: 0.586

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.58
PhyloP100		-0.20
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: rs2338104; hg19: chr12-109895168;