2-95382419-C-G

Variant names:

• chr2-95382419-C-G
• rs774695030
• NM_013434.5:c.598C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013434.5(KCNIP3):​c.598C>G​(p.Arg200Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict 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. R200C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNIP3 NM_013434.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP3	NM_013434.5	c.598C>G	p.Arg200Gly	missense_variant	Exon 7 of 9	ENST00000295225.10	NP_038462.1
KCNIP3	NM_001034914.2	c.520C>G	p.Arg174Gly	missense_variant	Exon 6 of 8		NP_001030086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNIP3	ENST00000295225.10	c.598C>G	p.Arg200Gly	missense_variant	Exon 7 of 9	1	NM_013434.5	ENSP00000295225.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	0.0071	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.079	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.1	L;.;.
PhyloP100		0.57
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.3	D;.;D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;.;D
Sift4G	Uncertain	0.026	D;D;D
Polyphen		0.41	B;.;P
Vest4		0.57
MutPred		0.48		Loss of stability (P = 0.0664);Loss of stability (P = 0.0664);.;
MVP		0.45
MPC		1.3
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.76
gMVP		0.78
Mutation Taster		=52/48	polymorphism

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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Other links and lift over

dbSNP: rs774695030; hg19: chr2-96048167;