rs6663

Positions:

• chr12-109448798-G-A

Variant summary

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

The ENST00000228495.11(KCTD10):​c.*2797C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,182 control chromosomes in the GnomAD database, including 3,287 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 0.20 (3287 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: KCTD10 ENST00000228495.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD10	NM_031954.5	c.*2797C>T		3_prime_UTR_variant	7/7	ENST00000228495.11	NP_114160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD10	ENST00000228495.11	c.*2797C>T		3_prime_UTR_variant	7/7	1	NM_031954.5	ENSP00000228495	P1
MYO1H	ENST00000543960.1	c.*98+1518G>A		intron_variant, NMD_transcript_variant		4		ENSP00000474025

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30857 AN: 152062 Hom.: 3288 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.203 AC: 30874 AN: 152180 Hom.: 3287 Cov.: 33 AF XY: 0.199 AC XY: 14831 AN XY: 74398

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.231

Alfa AF: 0.249 Hom.: 4486

Bravo AF: 0.207

Asia WGS AF: 0.199 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.9
DANN	Benign	0.84

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: rs6663; hg19: chr12-109886603;