NM_000890.5:c.834T>C

Variant names:

• chr11-128912107-T-C
• rs7118833
• NM_000890.5:c.834T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000890.5(KCNJ5):​c.834T>C​(p.His278His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,613,232 control chromosomes in the GnomAD database, including 549,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (54483 hom., cov: 33)
  • Exomes 𝑓: 0.82 (495084 hom.)
• Consequence: KCNJ5 NM_000890.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -1.09
• Publications: 25 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, ClinGen, Labcorp Genetics (formerly Invitae)
• Andersen-Tawil syndrome

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

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

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 11-128912107-T-C is Benign according to our data. Variant chr11-128912107-T-C is described in ClinVar as Benign. ClinVar VariationId is 137992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ5	NM_000890.5	MANE Select	c.834T>C	p.His278His	synonymous	Exon 2 of 3	NP_000881.3
	KCNJ5	NM_001354169.2		c.834T>C	p.His278His	synonymous	Exon 3 of 4	NP_001341098.1	P48544

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ5	ENST00000529694.6	TSL:1 MANE Select	c.834T>C	p.His278His	synonymous	Exon 2 of 3	ENSP00000433295.1	P48544
	KCNJ5	ENST00000338350.4	TSL:1	c.834T>C	p.His278His	synonymous	Exon 3 of 4	ENSP00000339960.4	P48544
	KCNJ5	ENST00000533599.1	TSL:1	c.834T>C	p.His278His	synonymous	Exon 1 of 2	ENSP00000434266.1	P48544

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128469 AN: 152012 Hom.: 54439 Cov.: 33

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.858

GnomAD2 exomes AF: 0.839 AC: 208357 AN: 248472 AF XY: 0.842

Gnomad AFR exome AF: 0.898

Gnomad AMR exome AF: 0.814

Gnomad ASJ exome AF: 0.848

Gnomad EAS exome AF: 0.880

Gnomad FIN exome AF: 0.793

Gnomad NFE exome AF: 0.824

Gnomad OTH exome AF: 0.836

GnomAD4 exome AF: 0.823 AC: 1201885 AN: 1461102 Hom.: 495084 Cov.: 47 AF XY: 0.826 AC XY: 600301 AN XY: 726848

African (AFR) AF: 0.903 AC: 30216 AN: 33476

American (AMR) AF: 0.813 AC: 36355 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 22145 AN: 26134

East Asian (EAS) AF: 0.872 AC: 34631 AN: 39700

South Asian (SAS) AF: 0.890 AC: 76739 AN: 86254

European-Finnish (FIN) AF: 0.789 AC: 41827 AN: 52988

Middle Eastern (MID) AF: 0.885 AC: 5107 AN: 5768

European-Non Finnish (NFE) AF: 0.814 AC: 904835 AN: 1111684

Other (OTH) AF: 0.829 AC: 50030 AN: 60376

GnomAD4 genome AF: 0.845 AC: 128568 AN: 152130 Hom.: 54483 Cov.: 33 AF XY: 0.846 AC XY: 62918 AN XY: 74380

African (AFR) AF: 0.895 AC: 37157 AN: 41508

American (AMR) AF: 0.837 AC: 12799 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2916 AN: 3466

East Asian (EAS) AF: 0.880 AC: 4541 AN: 5162

South Asian (SAS) AF: 0.893 AC: 4309 AN: 4826

European-Finnish (FIN) AF: 0.795 AC: 8429 AN: 10596

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55571 AN: 67958

Other (OTH) AF: 0.858 AC: 1815 AN: 2116

Alfa AF: 0.828 Hom.: 19455

Bravo AF: 0.849

Asia WGS AF: 0.883 AC: 3065 AN: 3474

EpiCase AF: 0.833

EpiControl AF: 0.833

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	2	Familial hyperaldosteronism type III (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Long QT syndrome (1)
-	-	1	Long QT syndrome 13 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.72
DANN	Benign	0.58
PhyloP100		-1.1
Mutation Taster		=93/7	polymorphism (auto)

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: rs7118833; hg19: chr11-128782002;