11-65593824-C-T

Variant names:

• chr11-65593824-C-T
• rs751500403
• NM_033347.2:c.370G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033347.2(KCNK7):​c.370G>A​(p.Val124Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,424,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V124L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KCNK7 NM_033347.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039247632).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033347.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK7	NM_033347.2	MANE Select	c.370G>A	p.Val124Ile	missense	Exon 2 of 3	NP_203133.1	Q9Y2U2-1
	KCNK7	NM_005714.2		c.370G>A	p.Val124Ile	missense	Exon 2 of 2	NP_005705.1	Q9Y2U2-3
	KCNK7	NM_033348.2		c.370G>A	p.Val124Ile	missense	Exon 2 of 4	NP_203134.1	Q9Y2U2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK7	ENST00000340313.5	TSL:1 MANE Select	c.370G>A	p.Val124Ile	missense	Exon 2 of 3	ENSP00000344820.5	Q9Y2U2-1
	KCNK7	ENST00000394216.6	TSL:1	c.370G>A	p.Val124Ile	missense	Exon 2 of 2	ENSP00000377764.2	Q9Y2U2-3
	KCNK7	ENST00000342202.8	TSL:1	c.370G>A	p.Val124Ile	missense	Exon 2 of 3	ENSP00000343923.4	Q9Y2U2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000463 AC: 1 AN: 216146 AF XY: 0.00000843

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000103

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1424056 Hom.: 0 Cov.: 32 AF XY: 0.00000426 AC XY: 3 AN XY: 704384

African (AFR) AF: 0.00 AC: 0 AN: 32212

American (AMR) AF: 0.00 AC: 0 AN: 39214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24188

East Asian (EAS) AF: 0.00 AC: 0 AN: 39162

South Asian (SAS) AF: 0.00 AC: 0 AN: 82374

European-Finnish (FIN) AF: 0.0000197 AC: 1 AN: 50678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1091988

Other (OTH) AF: 0.00 AC: 0 AN: 58632

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.7
DANN	Benign	0.81
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.94	L
PhyloP100		-1.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.046
Sift	Benign	0.53	T
Sift4G	Benign	0.92	T
Polyphen		0.0050	B
Vest4		0.10
MutPred		0.40		Loss of ubiquitination at K119 (P = 0.1343)
MVP		0.26
MPC		0.021
ClinPred		0.096	T
GERP RS		3.6
PromoterAI		0.044	Neutral
Varity_R		0.029
gMVP		0.26
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs751500403; hg19: chr11-65361295;