Genetic Variant KCTD10:c.723+767T>A (chr12-109455351-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031954.5(KCTD10):c.723+767T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 151,744 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 30)

Consequence

KCTD10
NM_031954.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.89

Publications

19 publications found

Variant links:

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]

KCTD10 links:

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)

MYO1H links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCTD10	NM_031954.5	MANE Select	c.723+767T>A	intron	N/A	NP_114160.1	Q9H3F6-1
KCTD10	NM_001317395.2		c.726+767T>A	intron	N/A	NP_001304324.1
KCTD10	NM_001317399.2		c.654+767T>A	intron	N/A	NP_001304328.1	Q9H3F6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCTD10	ENST00000228495.11	TSL:1 MANE Select	c.723+767T>A	intron	N/A	ENSP00000228495.6	Q9H3F6-1
KCTD10	ENST00000540411.5	TSL:1	c.645+767T>A	intron	N/A	ENSP00000441672.1	F5GWA4
KCTD10	ENST00000538161.5	TSL:1	n.620+767T>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151744

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74094

show subpopulations

African (AFR)

AF:

0.0000969

AC:

AN:

41278

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67940

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

6373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.18

(source)

DANN

Benign

0.52

PhyloP100

-1.9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over