rs767022101

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-101828237-C-T
• chr10-101828237-C-A
• chr10-101828237-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173191.3(KCNIP2):​c.511G>A​(p.Val171Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,874 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: KCNIP2 NM_173191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34986943).

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>A	p.Val171Met	missense	Exon 7 of 10	NP_775283.1	Q9NS61-1
	KCNIP2	NM_014591.5		c.556G>A	p.Val186Met	missense	Exon 7 of 10	NP_055406.2
	KCNIP2	NM_173192.3		c.457G>A	p.Val153Met	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>A	p.Val171Met	missense	Exon 7 of 10	ENSP00000349055.2	Q9NS61-1
	KCNIP2	ENST00000461105.5	TSL:1	c.556G>A	p.Val186Met	missense	Exon 7 of 10	ENSP00000420040.1	Q9NS61-6
	KCNIP2	ENST00000358038.7	TSL:1	c.457G>A	p.Val153Met	missense	Exon 6 of 9	ENSP00000350733.3	Q9NS61-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251438 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727232

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	0.0034	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.26
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.093	T
Polyphen		0.77	P
Vest4		0.52
MutPred		0.47		Gain of phosphorylation at T176 (P = 0.1227)
MVP		0.79
MPC		1.5
ClinPred		0.92	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.60
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;