rs10774708

Positions:

• chr12-109455351-A-G
• chr12-109455351-A-T

Variant summary

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

The NM_031954.5(KCTD10):​c.723+767T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,820 control chromosomes in the GnomAD database, including 25,925 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 (25923 hom., cov: 30)
  • Exomes 𝑓: 0.38 (2 hom.)
• Consequence: KCTD10 NM_031954.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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]

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 (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD10	NM_031954.5	c.723+767T>C		intron_variant		ENST00000228495.11	NP_114160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD10	ENST00000228495.11	c.723+767T>C		intron_variant		1	NM_031954.5	ENSP00000228495	P1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86901 AN: 151686 Hom.: 25877 Cov.: 30

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.586

GnomAD4 exome AF: 0.375 AC: 6 AN: 16 Hom.: 2 AF XY: 0.333 AC XY: 4 AN XY: 12

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.573 AC: 87009 AN: 151804 Hom.: 25923 Cov.: 30 AF XY: 0.564 AC XY: 41854 AN XY: 74186

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.587

Alfa AF: 0.497 Hom.: 2421

Bravo AF: 0.587

Asia WGS AF: 0.414 AC: 1440 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	0.21
DANN	Benign	0.42

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: rs10774708; hg19: chr12-109893156;