rs1477117

Variant names:

• chr12-109450974-G-A
• rs1477117
• NM_031954.5:c.*621C>T

Variant summary

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

The NM_031954.5(KCTD10):​c.*621C>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 0.135 in 152,394 control chromosomes in the GnomAD database, including 1,593 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 0.13 (1592 hom., cov: 32)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: KCTD10 NM_031954.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD10	NM_031954.5	c.*621C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000228495.11	NP_114160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD10	ENST00000228495	c.*621C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_031954.5	ENSP00000228495.6

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20526 AN: 151990 Hom.: 1596 Cov.: 32

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0992

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.133 AC: 38 AN: 286 Hom.: 1 Cov.: 0 AF XY: 0.152 AC XY: 24 AN XY: 158

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.0909

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.135 AC: 20523 AN: 152108 Hom.: 1592 Cov.: 32 AF XY: 0.131 AC XY: 9710 AN XY: 74360

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0992

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.151

Alfa AF: 0.177 Hom.: 3170

Bravo AF: 0.137

Asia WGS AF: 0.144 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1477117; hg19: chr12-109888779;