Variant 19-43767668-T-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_002250.3(KCNN4):c.1159A>C(p.Ser387Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KCNN4
NM_002250.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.144

Variant links:

Genes affected

KCNN4 (HGNC:6293): (potassium calcium-activated channel subfamily N member 4) The protein encoded by this gene is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization, which promotes calcium influx. The encoded protein may be part of the predominant calcium-activated potassium channel in T-lymphocytes. This gene is similar to other KCNN family potassium channel genes, but it differs enough to possibly be considered as part of a new subfamily. [provided by RefSeq, Jul 2008]

KCNN4 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=0.11851174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCNN4	NM_002250.3 linkuse as main transcript	c.1159A>C	p.Ser387Arg	missense_variant	8/9	ENST00000648319.1	NP_002241.1
KCNN4	XM_005258882.3 linkuse as main transcript	c.1063A>C	p.Ser355Arg	missense_variant	7/8		XP_005258939.1
KCNN4	XM_005258883.3 linkuse as main transcript	c.970A>C	p.Ser324Arg	missense_variant	8/9		XP_005258940.1
KCNN4	XM_047438794.1 linkuse as main transcript	c.487A>C	p.Ser163Arg	missense_variant	6/7		XP_047294750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN4	ENST00000648319.1 linkuse as main transcript	c.1159A>C	p.Ser387Arg	missense_variant	8/9		NM_002250.3	ENSP00000496939	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KCNN4-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2024

The KCNN4 c.1159A>C variant is predicted to result in the amino acid substitution p.Ser387Arg. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.34

T;T;T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.76

T;.;T;T

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Pathogenic

1.4

MutationAssessor

Benign

1.7

.;L;.;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.1

.;.;.;N

REVEL

Uncertain

0.34

Sift

Benign

0.18

.;.;.;T

Sift4G

Uncertain

0.0090

D;.;T;T

Polyphen

0.36

.;B;.;B

Vest4

0.20, 0.21

MutPred

0.31

.;Gain of catalytic residue at S387 (P = 0.0121);.;Gain of catalytic residue at S387 (P = 0.0121);

MVP

0.89

MPC

0.86

ClinPred

0.086

GERP RS

-0.16

Varity_R

0.25

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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