rs9943689

Positions:

• chr12-109452534-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.724-721C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,198 control chromosomes in the GnomAD database, including 2,902 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 (2902 hom., cov: 33)
• Consequence: KCTD10 NM_031954.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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 (HGNC:):

MYO1H (HGNC:13879): (myosin IH) Predicted to enable actin filament binding activity and microfilament motor activity. Predicted to be involved in actin filament organization and vesicle transport along actin filament. Predicted to be part of myosin complex. Predicted to be active in several cellular components, including actin cytoskeleton; microvillus; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD10	NM_031954.5	c.724-721C>T		intron_variant		ENST00000228495.11	NP_114160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD10	ENST00000228495.11	c.724-721C>T		intron_variant		1	NM_031954.5	ENSP00000228495.6

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28858 AN: 152080 Hom.: 2906 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.190 AC: 28857 AN: 152198 Hom.: 2902 Cov.: 33 AF XY: 0.187 AC XY: 13881 AN XY: 74414

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.206

Alfa AF: 0.226 Hom.: 2242

Bravo AF: 0.193

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.34
DANN	Benign	0.44

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: rs9943689; hg19: chr12-109890339;