12-109450974-G-A

Variant names:

• chr12-109450974-G-A
• rs1477117
• ENST00000545759.5:n.4352C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000545759.5(KCTD10):​n.4352C>T variant causes a non coding transcript exon 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 ENST00000545759.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 24 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000545759.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD10	NM_031954.5	MANE Select	c.*621C>T		3_prime_UTR	Exon 7 of 7	NP_114160.1
	KCTD10	NR_133897.2		n.1431C>T		non_coding_transcript_exon	Exon 6 of 6
	KCTD10	NR_133898.2		n.1387C>T		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD10	ENST00000545759.5	TSL:1	n.4352C>T		non_coding_transcript_exon	Exon 2 of 2
	KCTD10	ENST00000228495.11	TSL:1 MANE Select	c.*621C>T		3_prime_UTR	Exon 7 of 7	ENSP00000228495.6
	KCTD10	ENST00000440541.6	TSL:2	n.*1159C>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000390321.2

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

African (AFR) AF: 0.100 AC: 1 AN: 10

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 1 AN: 8

East Asian (EAS) AF: 0.100 AC: 1 AN: 10

South Asian (SAS) AF: 0.333 AC: 2 AN: 6

European-Finnish (FIN) AF: 0.0909 AC: 2 AN: 22

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.137 AC: 28 AN: 204

Other (OTH) AF: 0.167 AC: 3 AN: 18

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

African (AFR) AF: 0.0564 AC: 2339 AN: 41494

American (AMR) AF: 0.144 AC: 2207 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 661 AN: 3466

East Asian (EAS) AF: 0.136 AC: 702 AN: 5160

South Asian (SAS) AF: 0.137 AC: 661 AN: 4820

European-Finnish (FIN) AF: 0.0992 AC: 1050 AN: 10580

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12337 AN: 67988

Other (OTH) AF: 0.151 AC: 319 AN: 2112

Alfa AF: 0.173 Hom.: 3854

Bravo AF: 0.137

Asia WGS AF: 0.144 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.65
PhyloP100		0.085
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs1477117; hg19: chr12-109888779;