dbSNP rs1477117: KCTD10:n.4352C>T (chr12-109450974-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850

Publications

24 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:

Genome browser will be placed here

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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD10	NM_031954.5 link	c.*621C>T		3_prime_UTR_variant	Exon 7 of 7	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.*621C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_031954.5	ENSP00000228495.6		Q9H3F6-1

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20526

AN:

151990

Hom.:

1596

Cov.:

show subpopulations

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:

AN:

286

Hom.:

Cov.:

AF XY:

0.152

AC XY:

AN XY:

158

show subpopulations

African (AFR)

AF:

0.100

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

AN:

East Asian (EAS)

AF:

0.100

AC:

AN:

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AF:

0.0909

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.137

AC:

AN:

204

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.135

AC:

20523

AN:

152108

Hom.:

1592

Cov.:

AF XY:

0.131

AC XY:

9710

AN XY:

74360

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.181

AC:

12337

AN:

67988

Other (OTH)

AF:

0.151

AC:

319

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

898

1796

2695

3593

4491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.173

Hom.:

3854

Bravo

AF:

0.137

Asia WGS

AF:

0.144

AC:

502

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.7

(source)

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)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over