10-101828237-C-G

Variant names:

• chr10-101828237-C-G
• rs767022101
• NM_173191.3:c.511G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173191.3(KCNIP2):​c.511G>C​(p.Val171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. V171M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNIP2 NM_173191.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 3 publications found

Genes affected

KCNIP2 (HGNC:15522): (potassium voltage-gated channel interacting protein 2) This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belongs to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified from this gene. [provided by RefSeq, Jul 2008]

KCNIP2-AS1 (HGNC:48680): (KCNIP2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24957573).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173191.3. 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
	KCNIP2	NM_173191.3	MANE Select	c.511G>C	p.Val171Leu	missense	Exon 7 of 10	NP_775283.1	Q9NS61-1
	KCNIP2	NM_014591.5		c.556G>C	p.Val186Leu	missense	Exon 7 of 10	NP_055406.2
	KCNIP2	NM_173192.3		c.457G>C	p.Val153Leu	missense	Exon 6 of 9	NP_775284.1	Q9NS61-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP2	ENST00000356640.7	TSL:1 MANE Select	c.511G>C	p.Val171Leu	missense	Exon 7 of 10	ENSP00000349055.2	Q9NS61-1
	KCNIP2	ENST00000461105.5	TSL:1	c.556G>C	p.Val186Leu	missense	Exon 7 of 10	ENSP00000420040.1	Q9NS61-6
	KCNIP2	ENST00000358038.7	TSL:1	c.457G>C	p.Val153Leu	missense	Exon 6 of 9	ENSP00000350733.3	Q9NS61-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.029
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.95	L
PhyloP100		1.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.089
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.056	T
Polyphen		0.0010	B
Vest4		0.53
MutPred		0.46		Loss of loop (P = 0.2237)
MVP		0.71
MPC		0.69
ClinPred		0.87	D
GERP RS		5.1
Varity_R		0.15
gMVP		0.60
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs767022101; hg19: chr10-103587994;