Genetic Variant KCNG3:p.Glu57Lys (chr2-42493333-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_133329.6(KCNG3):c.169G>A(p.Glu57Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,488 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E57Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KCNG3
NM_133329.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.82

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32044196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNG3	NM_133329.6 link	c.169G>A	p.Glu57Lys	missense_variant	Exon 1 of 2	ENST00000306078.2	NP_579875.1	Q8TAE7-1
KCNG3	NM_172344.3 link	c.169G>A	p.Glu57Lys	missense_variant	Exon 1 of 2		NP_758847.1	Q8TAE7-2
KCNG3	XR_007069666.1 link	n.650G>A		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNG3	ENST00000306078.2 link	c.169G>A	p.Glu57Lys	missense_variant	Exon 1 of 2	1	NM_133329.6	ENSP00000304127.1		Q8TAE7-1
KCNG3	ENST00000394973.4 link	c.169G>A	p.Glu57Lys	missense_variant	Exon 1 of 2	1		ENSP00000378424.4		Q8TAE7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451488

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33202

American (AMR)

AF:

0.00

AC:

AN:

43756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25796

East Asian (EAS)

AF:

0.00

AC:

AN:

39290

South Asian (SAS)

AF:

0.00

AC:

AN:

85012

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107382

Other (OTH)

AF:

0.00

AC:

AN:

59944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.0048

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;D

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.5

L;L

PhyloP100

5.8

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.3

N;N

REVEL

Uncertain

0.41

Sift

Benign

0.47

T;T

Sift4G

Benign

0.83

T;T

Polyphen

0.97

D;P

Vest4

0.25

MutPred

0.41

Gain of ubiquitination at E57 (P = 0.0117);Gain of ubiquitination at E57 (P = 0.0117);

MVP

0.87

MPC

1.9

ClinPred

0.97

GERP RS

3.3

Varity_R

0.22

gMVP

0.72

Mutation Taster

=64/36

polymorphism

(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