chr11-65593835-G-A

Position:

• chr11-65593835-G-A

Variant summary

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

The NM_033347.2(KCNK7):​c.359C>T​(p.Ala120Val) 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. 14/21 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: KCNK7 NM_033347.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0971922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK7	NM_033347.2	c.359C>T	p.Ala120Val	missense_variant	2/3	ENST00000340313.5	NP_203133.1
KCNK7	NM_005714.2	c.359C>T	p.Ala120Val	missense_variant	2/2		NP_005705.1
KCNK7	NM_033348.2	c.359C>T	p.Ala120Val	missense_variant	2/4		NP_203134.1
KCNK7	NM_033455.2	c.359C>T	p.Ala120Val	missense_variant	2/3		NP_258416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK7	ENST00000340313.5	c.359C>T	p.Ala120Val	missense_variant	2/3	1	NM_033347.2	ENSP00000344820.5
KCNK7	ENST00000394216.6	c.359C>T	p.Ala120Val	missense_variant	2/2	1		ENSP00000377764.2
KCNK7	ENST00000342202.8	c.359C>T	p.Ala120Val	missense_variant	2/3	1		ENSP00000343923.4
KCNK7	ENST00000394217.6	c.359C>T	p.Ala120Val	missense_variant	2/4	1		ENSP00000377765.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000507 AC: 1 AN: 197388 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 108154

Gnomad AFR exome AF: 0.0000698

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ESP6500AA AF: 0.000229 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000831 AC: 1

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

Apr 10, 2023

The c.359C>T (p.A120V) alteration is located in exon 2 (coding exon 2) of the KCNK7 gene. This alteration results from a C to T substitution at nucleotide position 359, causing the alanine (A) at amino acid position 120 to be replaced by a valine (V). 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	0.074
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	.;.;.;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.65	.;T;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.097	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.36	N;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.99	N;N;N;N
REVEL	Benign	0.015
Sift	Benign	0.086	T;T;T;T
Sift4G	Benign	0.074	T;T;T;T
Polyphen		0.20	B;B;B;B
Vest4		0.23
MVP		0.25
MPC		0.025
ClinPred		0.24	T
GERP RS		2.4
Varity_R		0.059
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs142989265; hg19: chr11-65361306;