rs9943689

Variant names:

• chr12-109452534-G-A
• rs9943689
• NM_031954.5:c.724-721C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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]

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]

MYO1H Gene-Disease associations (from GenCC):

• congenital central hypoventilation syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• central hypoventilation syndrome, congenital, 2, and autonomic dysfunction

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031954.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD10	NM_031954.5	MANE Select	c.724-721C>T		intron	N/A	NP_114160.1	Q9H3F6-1
	KCTD10	NM_001317395.2		c.727-721C>T		intron	N/A	NP_001304324.1
	KCTD10	NM_001317399.2		c.655-721C>T		intron	N/A	NP_001304328.1	Q9H3F6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD10	ENST00000228495.11	TSL:1 MANE Select	c.724-721C>T		intron	N/A	ENSP00000228495.6	Q9H3F6-1
	KCTD10	ENST00000540411.5	TSL:1	c.646-721C>T		intron	N/A	ENSP00000441672.1	F5GWA4
	KCTD10	ENST00000538161.5	TSL:1	n.621-721C>T		intron	N/A

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

African (AFR) AF: 0.124 AC: 5151 AN: 41532

American (AMR) AF: 0.190 AC: 2901 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3470

East Asian (EAS) AF: 0.116 AC: 598 AN: 5170

South Asian (SAS) AF: 0.229 AC: 1102 AN: 4820

European-Finnish (FIN) AF: 0.157 AC: 1668 AN: 10596

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15805 AN: 67992

Other (OTH) AF: 0.206 AC: 436 AN: 2116

Alfa AF: 0.227 Hom.: 2461

Bravo AF: 0.193

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.34
DANN	Benign	0.44
PhyloP100		-1.0
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: rs9943689; hg19: chr12-109890339;