11-128912083-T-C

Variant names:

• chr11-128912083-T-C
• rs7118824
• NM_000890.5:c.810T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_000890.5(KCNJ5):​c.810T>C​(p.Leu270Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L270L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNJ5 NM_000890.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.91
• Publications: 34 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: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 11-128912083-T-C is Benign according to our data. Variant chr11-128912083-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1130667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.91 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ5	NM_000890.5	c.810T>C	p.Leu270Leu	synonymous_variant	Exon 2 of 3	ENST00000529694.6	NP_000881.3
KCNJ5	NM_001354169.2	c.810T>C	p.Leu270Leu	synonymous_variant	Exon 3 of 4		NP_001341098.1
KCNJ5	XM_011542810.4	c.810T>C	p.Leu270Leu	synonymous_variant	Exon 2 of 3		XP_011541112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ5	ENST00000529694.6	c.810T>C	p.Leu270Leu	synonymous_variant	Exon 2 of 3	1	NM_000890.5	ENSP00000433295.1
KCNJ5	ENST00000338350.4	c.810T>C	p.Leu270Leu	synonymous_variant	Exon 3 of 4	1		ENSP00000339960.4
KCNJ5	ENST00000533599.1	c.810T>C	p.Leu270Leu	synonymous_variant	Exon 1 of 2	1		ENSP00000434266.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 88646

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Long QT syndrome 13;C3838758:Familial hyperaldosteronism type III Benign:1

Mar 03, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Long QT syndrome Benign:1

Mar 09, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.0
DANN	Benign	0.71
PhyloP100		1.9

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: rs7118824; hg19: chr11-128781978;