rs10774708

Variant names:

• chr12-109455351-A-G
• rs10774708
• NM_031954.5:c.723+767T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-109455351-A-G
• chr12-109455351-A-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.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
• Publications: 19 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 (AFR) allele frequency at 95% confidence interval = 0.727 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.723+767T>C		intron	N/A	NP_114160.1	Q9H3F6-1
	KCTD10	NM_001317395.2		c.726+767T>C		intron	N/A	NP_001304324.1
	KCTD10	NM_001317399.2		c.654+767T>C		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.723+767T>C		intron	N/A	ENSP00000228495.6	Q9H3F6-1
	KCTD10	ENST00000540411.5	TSL:1	c.645+767T>C		intron	N/A	ENSP00000441672.1	F5GWA4
	KCTD10	ENST00000538161.5	TSL:1	n.620+767T>C		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.125 AC: 1 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.833 AC: 5 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.734 AC: 30365 AN: 41386

American (AMR) AF: 0.507 AC: 7743 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1865 AN: 3464

East Asian (EAS) AF: 0.345 AC: 1786 AN: 5172

South Asian (SAS) AF: 0.410 AC: 1969 AN: 4806

European-Finnish (FIN) AF: 0.463 AC: 4862 AN: 10500

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.537 AC: 36498 AN: 67912

Other (OTH) AF: 0.587 AC: 1230 AN: 2096

Alfa AF: 0.601 Hom.: 6373

Bravo AF: 0.587

Asia WGS AF: 0.414 AC: 1440 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	0.21
DANN	Benign	0.42
PhyloP100		-1.9
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: rs10774708; hg19: chr12-109893156; COSMIC: COSV107994083; COSMIC: COSV107994083;