chr4-20850664-C-T

Variant names:

• chr4-20850664-C-T
• NM_025221.6:c.167G>A

Variant summary

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

The NM_025221.6(KCNIP4):​c.167G>A​(p.Ser56Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNIP4 NM_025221.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16
• Publications: 0 publications found

Genes affected

KCNIP4 (HGNC:30083): (potassium voltage-gated channel interacting protein 4) This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong 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. This protein member also interacts with presenilin. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

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=0.15982333).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025221.6. 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
	KCNIP4	NM_025221.6	MANE Select	c.167G>A	p.Ser56Asn	missense	Exon 3 of 9	NP_079497.2
	KCNIP4	NM_001363504.2		c.116G>A	p.Ser39Asn	missense	Exon 2 of 8	NP_001350433.1	Q3YAB7
	KCNIP4	NM_147183.3		c.104G>A	p.Ser35Asn	missense	Exon 2 of 8	NP_671712.1	Q6PIL6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	ENST00000382152.7	TSL:5 MANE Select	c.167G>A	p.Ser56Asn	missense	Exon 3 of 9	ENSP00000371587.2	Q6PIL6-1
	KCNIP4	ENST00000382149.9	TSL:1	c.116G>A	p.Ser39Asn	missense	Exon 2 of 8	ENSP00000494651.1	Q3YAB7
	KCNIP4	ENST00000382150.8	TSL:1	c.104G>A	p.Ser35Asn	missense	Exon 2 of 8	ENSP00000371585.4	Q6PIL6-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.11
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.049
Sift	Benign	0.099	T
Sift4G	Benign	0.15	T
Polyphen		0.0030	B
Vest4		0.22
MutPred		0.24		Loss of phosphorylation at S31 (P = 0.0457)
MVP		0.76
MPC		0.49
ClinPred		0.51	D
GERP RS		4.6
PromoterAI		0.030	Neutral
Varity_R		0.10
gMVP		0.30
Mutation Taster		=288/12	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

hg19: chr4-20852287;