Variant 1-215573799-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM2PP3_ModerateBS2

The NM_016121.5(KCTD3):c.97A>G(p.Arg33Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000351 in 1,425,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

KCTD3
NM_016121.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.61

Variant links:

Genes affected

KCTD3 (HGNC:21305): (potassium channel tetramerization domain containing 3) This gene encodes a member of the potassium channel tetramerization-domain containing (KCTD) protein family. Members of this protein family regulate the biophysical characteristics of ion channels. In mouse, this protein interacts with hyperpolarization-activated cyclic nucleotide-gated channel complex 3 and enhances its cell surface expression and current density. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

KCTD3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.891

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD3	NM_016121.5 link	c.97A>G	p.Arg33Gly	missense_variant	2/18	ENST00000259154.9	NP_057205.2	Q9Y597-1
KCTD3	NM_001319294.2 link	c.97A>G	p.Arg33Gly	missense_variant	2/18		NP_001306223.1	Q9Y597-2
KCTD3	NM_001319295.2 link	c.-282A>G		5_prime_UTR_variant	2/18		NP_001306224.1	Q9Y597
KCTD3	XM_047422104.1 link	c.-649A>G		upstream_gene_variant			XP_047278060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD3	ENST00000259154.9 link	c.97A>G	p.Arg33Gly	missense_variant	2/18	1	NM_016121.5	ENSP00000259154.2		Q9Y597-1
KCTD3	ENST00000448333.1 link	c.13A>G	p.Arg5Gly	missense_variant	1/8	2		ENSP00000396726.1		H0Y566

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245328

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000351

AC:

AN:

1425452

Hom.:

Cov.:

AF XY:

0.00000422

AC XY:

AN XY:

710112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000369

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.97A>G (p.R33G) alteration is located in exon 2 (coding exon 2) of the KCTD3 gene. This alteration results from a A to G substitution at nucleotide position 97, causing the arginine (R) at amino acid position 33 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.36

MetaRNN

Pathogenic

0.89

MetaSVM

Uncertain

0.25

MutationAssessor

Pathogenic

3.2

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.88

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

0.25

Vest4

0.81

MutPred

0.75

Gain of methylation at R28 (P = 0.0737);

MVP

0.70

MPC

1.3

ClinPred

0.99

GERP RS

5.2

Varity_R

0.82

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over