chr1-233671330-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 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

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

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=0.24342352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK1	NM_002245.4	c.811C>A	p.His271Asn	missense_variant	Exon 3 of 3	ENST00000366621.8	NP_002236.1
KCNK1	XM_011544184.3	c.607C>A	p.His203Asn	missense_variant	Exon 5 of 5		XP_011542486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK1	ENST00000366621.8	c.811C>A	p.His271Asn	missense_variant	Exon 3 of 3	1	NM_002245.4	ENSP00000355580.3
KCNK1	ENST00000446915.1	c.565C>A	p.His189Asn	missense_variant	Exon 3 of 3	3		ENSP00000409626.1
KCNK1	ENST00000366620.5	n.1178C>A		non_coding_transcript_exon_variant	Exon 6 of 6	2
KCNK1	ENST00000472190.5	n.813C>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.811C>A (p.H271N) alteration is located in exon 3 (coding exon 3) of the KCNK1 gene. This alteration results from a C to A substitution at nucleotide position 811, causing the histidine (H) at amino acid position 271 to be replaced by an asparagine (N). 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	0.098
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.35	T;T
Eigen	Benign	-0.034
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.64	N;N
REVEL	Benign	0.065
Sift	Benign	0.24	T;T
Sift4G	Benign	0.36	T;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

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: rs770054172; hg19: chr1-233807076; COSMIC: COSV100785659; COSMIC: COSV100785659;