11-65593845-C-T

Position:

• chr11-65593845-C-T

Variant summary

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

The NM_033347.2(KCNK7):​c.349G>A​(p.Gly117Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNK7 NM_033347.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.35

Genes affected

KCNK7 (HGNC:6282): (potassium two pore domain channel subfamily K member 7) This gene encodes a member of the superfamily of potassium channel proteins containing two pore-forming P domains. The product of this gene has not been shown to be a functional channel; however, it may require other non-pore-forming proteins for activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK7	NM_033347.2	c.349G>A	p.Gly117Ser	missense_variant	2/3	ENST00000340313.5	NP_203133.1
KCNK7	NM_005714.2	c.349G>A	p.Gly117Ser	missense_variant	2/2		NP_005705.1
KCNK7	NM_033348.2	c.349G>A	p.Gly117Ser	missense_variant	2/4		NP_203134.1
KCNK7	NM_033455.2	c.349G>A	p.Gly117Ser	missense_variant	2/3		NP_258416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK7	ENST00000340313.5	c.349G>A	p.Gly117Ser	missense_variant	2/3	1	NM_033347.2	ENSP00000344820.5
KCNK7	ENST00000394216.6	c.349G>A	p.Gly117Ser	missense_variant	2/2	1		ENSP00000377764.2
KCNK7	ENST00000342202.8	c.349G>A	p.Gly117Ser	missense_variant	2/3	1		ENSP00000343923.4
KCNK7	ENST00000394217.6	c.349G>A	p.Gly117Ser	missense_variant	2/4	1		ENSP00000377765.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.349G>A (p.G117S) alteration is located in exon 2 (coding exon 2) of the KCNK7 gene. This alteration results from a G to A substitution at nucleotide position 349, causing the glycine (G) at amino acid position 117 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.0040	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	.;.;.;T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.69	.;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L;L;L;L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N;N;D;N
REVEL	Benign	0.14
Sift	Benign	0.14	T;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.37
MutPred		0.44		Gain of glycosylation at G117 (P = 0.0064);Gain of glycosylation at G117 (P = 0.0064);Gain of glycosylation at G117 (P = 0.0064);Gain of glycosylation at G117 (P = 0.0064);
MVP		0.50
MPC		0.14
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.12
gMVP		0.52

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65361316;