rs1060503834

Variant names:

• chr11-128912116-CC-TG
• rs1060503834
• NM_000890.5:c.843_844delCCinsTG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PM1 PM2 BP6_Very_Strong

The NM_000890.5(KCNJ5):​c.843_844delCCinsTG​(p.Gln282Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNJ5 NM_000890.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.89

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM1: In a topological_domain Cytoplasmic (size 233) in uniprot entity KCNJ5_HUMAN there are 5 pathogenic changes around while only 1 benign (83%) in NM_000890.5
• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 11-128912116-CC-TG is Benign according to our data. Variant chr11-128912116-CC-TG is described in ClinVar as [Likely_benign]. Clinvar id is 412766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ5	NM_000890.5	c.843_844delCCinsTG	p.Gln282Glu	missense_variant		ENST00000529694.6	NP_000881.3
KCNJ5	NM_001354169.2	c.843_844delCCinsTG	p.Gln282Glu	missense_variant			NP_001341098.1
KCNJ5	XM_011542810.4	c.843_844delCCinsTG	p.Gln282Glu	missense_variant			XP_011541112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ5	ENST00000529694.6	c.843_844delCCinsTG	p.Gln282Glu	missense_variant		1	NM_000890.5	ENSP00000433295.1
KCNJ5	ENST00000338350.4	c.843_844delCCinsTG	p.Gln282Glu	missense_variant		1		ENSP00000339960.4
KCNJ5	ENST00000533599.1	c.843_844delCCinsTG	p.Gln282Glu	missense_variant		1		ENSP00000434266.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Long QT syndrome Benign:1

Nov 10, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype Benign:1

May 31, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1060503834; hg19: chr11-128782011;