Genetic Variant NM_031954.5:c.723+767T>C (chr12-109455351-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

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: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD10	NM_031954.5 link	c.723+767T>C		intron_variant	Intron 6 of 6	ENST00000228495.11	NP_114160.1	Q9H3F6-1A0A024RBJ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD10	ENST00000228495.11 link	c.723+767T>C		intron_variant	Intron 6 of 6	1	NM_031954.5	ENSP00000228495.6		Q9H3F6-1

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

86901

AN:

151686

Hom.:

25877

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.833

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.573

AC:

87009

AN:

151804

Hom.:

25923

Cov.:

AF XY:

0.564

AC XY:

41854

AN XY:

74186

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1762

3524

5285

7047

8809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.601

Hom.:

6373

Bravo

AF:

0.587

Asia WGS

AF:

0.414

AC:

1440

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.21

(source)

DANN

Benign

0.42

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over