Variant 2-42493085-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133329.6(KCNG3):c.417G>C(p.Glu139Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,411,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KCNG3
NM_133329.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.828

Variant links:

Genes affected

KCNG3 (HGNC:18306): (potassium voltage-gated channel modifier subfamily G member 3) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily G. This member is a gamma subunit functioning as a modulatory molecule. Alternative splicing results in two transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

KCNG3 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;

BP4

Computational evidence support a benign effect (MetaRNN=0.11820799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNG3	NM_133329.6 linkuse as main transcript	c.417G>C	p.Glu139Asp	missense_variant	1/2	ENST00000306078.2
KCNG3	NM_172344.3 linkuse as main transcript	c.417G>C	p.Glu139Asp	missense_variant	1/2
KCNG3	XR_007069666.1 linkuse as main transcript	n.898G>C		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNG3	ENST00000306078.2 linkuse as main transcript	c.417G>C	p.Glu139Asp	missense_variant	1/2	1	NM_133329.6	P1	Q8TAE7-1
KCNG3	ENST00000394973.4 linkuse as main transcript	c.417G>C	p.Glu139Asp	missense_variant	1/2	1			Q8TAE7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1411260

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698724

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.417G>C (p.E139D) alteration is located in exon 1 (coding exon 1) of the KCNG3 gene. This alteration results from a G to C substitution at nucleotide position 417, causing the glutamic acid (E) at amino acid position 139 to be replaced by an aspartic acid (D). 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

Benign

0.065

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.51

T;T

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.12

T;T

MetaSVM

Uncertain

0.073

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.85

N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.94

N;N

REVEL

Benign

0.24

Sift

Benign

0.20

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.048

B;B

Vest4

0.071

MutPred

0.15

Gain of helix (P = 0.2684);Gain of helix (P = 0.2684);

MVP

0.87

MPC

0.87

ClinPred

0.087

GERP RS

3.1

Varity_R

0.087

gMVP

0.69

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over