1-233671330-C-A

Variant names:

• chr1-233671330-C-A
• rs770054172
• NM_002245.4:c.811C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002245.4(KCNK1):​c.811C>A​(p.His271Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KCNK1 NM_002245.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.61
• Publications: 0 publications found

Genes affected

KCNK1 (HGNC:6272): (potassium two pore domain channel subfamily K member 1) This gene encodes one of the members 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24342352).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002245.4. 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
	KCNK1	NM_002245.4	MANE Select	c.811C>A	p.His271Asn	missense	Exon 3 of 3	NP_002236.1	O00180

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK1	ENST00000366621.8	TSL:1 MANE Select	c.811C>A	p.His271Asn	missense	Exon 3 of 3	ENSP00000355580.3	O00180
	KCNK1	ENST00000446915.1	TSL:3	c.565C>A	p.His189Asn	missense	Exon 3 of 3	ENSP00000409626.1	Q5T5E6
	KCNK1	ENST00000918244.1		c.448C>A	p.His150Asn	missense	Exon 3 of 3	ENSP00000588303.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.034
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.065
Sift	Benign	0.24	T
Sift4G	Benign	0.36	T
Polyphen		0.049	B
Vest4		0.43
MVP		0.38
MPC		0.45
ClinPred		0.48	T
GERP RS		6.0
Varity_R		0.17
gMVP		0.74
Mutation Taster		=70/30	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: rs770054172; hg19: chr1-233807076; COSMIC: COSV100785659; COSMIC: COSV100785659;