rs774695030

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-95382419-C-G
• chr2-95382419-C-T

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
• Publications: 0 publications found

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

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>G	p.Arg200Gly	missense	Exon 7 of 9	NP_038462.1	Q9Y2W7-1
	KCNIP3	NM_001034914.2		c.520C>G	p.Arg174Gly	missense	Exon 6 of 8	NP_001030086.1	Q9Y2W7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP3	ENST00000295225.10	TSL:1 MANE Select	c.598C>G	p.Arg200Gly	missense	Exon 7 of 9	ENSP00000295225.5	Q9Y2W7-1
	KCNIP3	ENST00000468529.1	TSL:1	c.520C>G	p.Arg174Gly	missense	Exon 6 of 8	ENSP00000417499.1	Q9Y2W7-3
	KCNIP3	ENST00000873168.1		c.625C>G	p.Arg209Gly	missense	Exon 7 of 9	ENSP00000543227.1

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 v4.9

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
M_CAP	Benign	0.079	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.57
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.026	D
Polyphen		0.41	B
Vest4		0.57
MutPred		0.48		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

Other links and lift over

dbSNP: rs774695030; hg19: chr2-96048167;