19-43767555-C-A

Position:

• chr19-43767555-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002250.3(KCNN4):​c.1272G>T​(p.Gln424His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNN4 NM_002250.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

Genes affected

KCNN4 (HGNC:6293): (potassium calcium-activated channel subfamily N member 4) The protein encoded by this gene is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization, which promotes calcium influx. The encoded protein may be part of the predominant calcium-activated potassium channel in T-lymphocytes. This gene is similar to other KCNN family potassium channel genes, but it differs enough to possibly be considered as part of a new subfamily. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25631347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN4	NM_002250.3	c.1272G>T	p.Gln424His	missense_variant	8/9	ENST00000648319.1	NP_002241.1
KCNN4	XM_005258882.3	c.1176G>T	p.Gln392His	missense_variant	7/8		XP_005258939.1
KCNN4	XM_005258883.3	c.1083G>T	p.Gln361His	missense_variant	8/9		XP_005258940.1
KCNN4	XM_047438794.1	c.600G>T	p.Gln200His	missense_variant	6/7		XP_047294750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN4	ENST00000648319.1	c.1272G>T	p.Gln424His	missense_variant	8/9		NM_002250.3	ENSP00000496939	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dehydrated hereditary stomatocytosis 2 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T;T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.51	T;.;T;T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Benign	1.9	.;M;.;M
MutationTaster	Benign	0.93	D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.55	.;.;.;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	.;.;.;D
Sift4G	Uncertain	0.0060	D;.;D;D
Polyphen		0.92	.;P;.;P
Vest4		0.19, 0.17
MutPred		0.073		.;Loss of glycosylation at P422 (P = 0.1003);.;Loss of glycosylation at P422 (P = 0.1003);
MVP		0.97
MPC		0.50
ClinPred		0.72	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-44271707;