11-65593159-G-C

Position:

• chr11-65593159-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033347.2(KCNK7):​c.770C>G​(p.Ser257Cys) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNK7 NM_033347.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0200

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048548937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK7	NM_033347.2	c.770C>G	p.Ser257Cys	missense_variant	3/3	ENST00000340313.5	NP_203133.1
KCNK7	NM_005714.2	c.*261C>G		3_prime_UTR_variant	2/2		NP_005705.1
KCNK7	NM_033348.2	c.*85C>G		3_prime_UTR_variant	4/4		NP_203134.1
KCNK7	NM_033455.2	c.*184C>G		3_prime_UTR_variant	3/3		NP_258416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK7	ENST00000340313.5	c.770C>G	p.Ser257Cys	missense_variant	3/3	1	NM_033347.2	ENSP00000344820.5

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

Oct 06, 2024

The c.770C>G (p.S257C) alteration is located in exon 3 (coding exon 3) of the KCNK7 gene. This alteration results from a C to G substitution at nucleotide position 770, causing the serine (S) at amino acid position 257 to be replaced by a cysteine (C). 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	0.084
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.5
DANN	Benign	0.81
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.71	N
REVEL	Benign	0.020
Sift	Benign	0.37	T
Sift4G	Benign	0.25	T
Polyphen		0.014	B
Vest4		0.084
MutPred		0.47		Loss of helix (P = 0.0376);
MVP		0.15
MPC		0.12
ClinPred		0.045	T
GERP RS		-1.9
Varity_R		0.044
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr11-65360630;