Genetic Variant KCNIP3:p.Arg200Cys (chr2-95382419-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_013434.5(KCNIP3):c.598C>T(p.Arg200Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,608,298 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

KCNIP3
NM_013434.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.570

Publications

0 publications found

Variant links:

Genes affected

KCNIP3 (HGNC:15523): (potassium voltage-gated channel interacting protein 3) This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins, which belong to the recoverin branch of the EF-hand superfamily. Members of this family are small calcium binding proteins containing EF-hand-like domains. They are integral subunit components of native Kv4 channel complexes that may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. The encoded protein also functions as a calcium-regulated transcriptional repressor, and interacts with presenilins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

KCNIP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013434.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP3	NM_013434.5	MANE Select	c.598C>T	p.Arg200Cys	missense	Exon 7 of 9	NP_038462.1	Q9Y2W7-1
	KCNIP3	NM_001034914.2		c.520C>T	p.Arg174Cys	missense	Exon 6 of 8	NP_001030086.1	Q9Y2W7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNIP3	ENST00000295225.10	TSL:1 MANE Select	c.598C>T	p.Arg200Cys	missense	Exon 7 of 9	ENSP00000295225.5	Q9Y2W7-1
KCNIP3	ENST00000468529.1	TSL:1	c.520C>T	p.Arg174Cys	missense	Exon 6 of 8	ENSP00000417499.1	Q9Y2W7-3
KCNIP3	ENST00000873168.1		c.625C>T	p.Arg209Cys	missense	Exon 7 of 9	ENSP00000543227.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

244966

AF XY:

0.0000225

show subpopulations

Gnomad AFR exome

AF:

0.0000636

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000893

AC:

AN:

1456184

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

724414

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33214

American (AMR)

AF:

0.00

AC:

AN:

44040

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25954

East Asian (EAS)

AF:

0.00

AC:

AN:

39270

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000991

AC:

AN:

1109688

Other (OTH)

AF:

0.00

AC:

AN:

60096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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

AF:

0.0000394

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.53

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.84

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.095

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.4

PhyloP100

0.57

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Polyphen

0.99

Vest4

0.62

MutPred

0.56

Loss of phosphorylation at T202 (P = 0.0815)

MVP

0.52

MPC

1.5

ClinPred

0.95

GERP RS

4.3

Varity_R

0.81

gMVP

0.78

Mutation Taster

=57/43

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over