chr14-88187979-C-A

Variant names:

• chr14-88187979-C-A
• NM_138317.3:c.999G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_138317.3(KCNK10):​c.999G>T​(p.Lys333Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNK10 NM_138317.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.10

Genes affected

KCNK10 (HGNC:6273): (potassium two pore domain channel subfamily K member 10) The protein encoded by this gene belongs to the family of potassium channel proteins containing two pore-forming P domains. This channel is an open rectifier which primarily passes outward current under physiological K+ concentrations, and is stimulated strongly by arachidonic acid and to a lesser degree by membrane stretching, intracellular acidification, and general anaesthetics. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 14-88187979-C-A is Benign according to our data. Variant chr14-88187979-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2681346.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK10	NM_138317.3	c.999G>T	p.Lys333Asn	missense_variant	Exon 6 of 7	ENST00000319231.10	NP_612190.1
KCNK10	NM_138318.3	c.999G>T	p.Lys333Asn	missense_variant	Exon 6 of 7		NP_612191.1
KCNK10	NM_021161.5	c.984G>T	p.Lys328Asn	missense_variant	Exon 6 of 7		NP_066984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK10	ENST00000319231.10	c.999G>T	p.Lys333Asn	missense_variant	Exon 6 of 7	1	NM_138317.3	ENSP00000312811.5
KCNK10	ENST00000312350.9	c.999G>T	p.Lys333Asn	missense_variant	Exon 6 of 7	1		ENSP00000310568.5
KCNK10	ENST00000340700.9	c.984G>T	p.Lys328Asn	missense_variant	Exon 6 of 7	1		ENSP00000343104.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma Benign:1

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Department of Clinical Pathology, School of Medicine, Fujita Health University

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.085	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.83
MutPred		0.38		Loss of ubiquitination at K328 (P = 0.0309);.;.;
MVP		0.72
MPC		1.3
ClinPred		0.89	D
GERP RS		5.8
Varity_R		0.47
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr14-88654323; COSMIC: COSV56642395;