rs1555144961

Variant names:

• chr11-128911670-C-G
• rs1555144961
• NM_000890.5:c.397C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-128911670-C-G
• chr11-128911670-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000890.5(KCNJ5):​c.397C>G​(p.Leu133Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L133F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KCNJ5 NM_000890.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.89
• Publications: 0 publications found

Genes affected

KCNJ5 (HGNC:6266): (potassium inwardly rectifying channel subfamily J member 5) This gene encodes an integral membrane protein which belongs to one of seven subfamilies of inward-rectifier potassium channel proteins called potassium channel subfamily J. The encoded protein is a subunit of the potassium channel which is homotetrameric. It is controlled by G-proteins and has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Naturally occurring mutations in this gene are associated with aldosterone-producing adenomas. [provided by RefSeq, Aug 2017]

KCNJ5 Gene-Disease associations (from GenCC):

• familial hyperaldosteronism type III

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• Andersen-Tawil syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• long QT syndrome 13

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• long QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29285204).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000890.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ5	NM_000890.5	MANE Select	c.397C>G	p.Leu133Val	missense	Exon 2 of 3	NP_000881.3
	KCNJ5	NM_001354169.2		c.397C>G	p.Leu133Val	missense	Exon 3 of 4	NP_001341098.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ5	ENST00000529694.6	TSL:1 MANE Select	c.397C>G	p.Leu133Val	missense	Exon 2 of 3	ENSP00000433295.1
	KCNJ5	ENST00000338350.4	TSL:1	c.397C>G	p.Leu133Val	missense	Exon 3 of 4	ENSP00000339960.4
	KCNJ5	ENST00000533599.1	TSL:1	c.397C>G	p.Leu133Val	missense	Exon 1 of 2	ENSP00000434266.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461894 Hom.: 0 Cov.: 58 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

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: 0.00000180 AC: 2 AN: 1112012

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Benign	0.14
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-0.25
Eigen_PC	Benign	0.0074
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.11	N
PhyloP100		4.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.050	N
REVEL	Uncertain	0.49
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.28	B
Vest4		0.40
MutPred		0.50		Gain of loop (P = 0.2045)
MVP		0.91
MPC		0.44
ClinPred		0.35	T
GERP RS		5.5
PromoterAI		0.084	Neutral
Varity_R		0.25
gMVP		0.91
Mutation Taster		=68/32	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: rs1555144961; hg19: chr11-128781565;