22-38426693-C-G

Variant names:

• chr22-38426693-C-G
• rs1063134
• NM_152868.3:c.*102G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152868.3(KCNJ4):​c.*102G>C variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNJ4 NM_152868.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.39
• Publications: 9 publications found

Genes affected

KCNJ4 (HGNC:6265): (potassium inwardly rectifying channel subfamily J member 4) Several different potassium channels are known to be involved with electrical signaling in the nervous system. One class is activated by depolarization whereas a second class is not. The latter are referred to as inwardly rectifying K+ channels, and they have a greater tendency to allow potassium to flow into the cell rather than out of it. This asymmetry in potassium ion conductance plays a key role in the excitability of muscle cells and neurons. The protein encoded by this gene is an integral membrane protein and member of the inward rectifier potassium channel family. The encoded protein has a small unitary conductance compared to other members of this protein family. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000228620 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152868.3. 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
	KCNJ4	NM_152868.3	MANE Select	c.*102G>C		3_prime_UTR	Exon 2 of 2	NP_690607.1	P48050
	KCNJ4	NM_004981.2		c.*102G>C		3_prime_UTR	Exon 2 of 2	NP_004972.1	P48050

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ4	ENST00000303592.3	TSL:1 MANE Select	c.*102G>C		3_prime_UTR	Exon 2 of 2	ENSP00000306497.3	P48050
	KCNJ4	ENST00000940563.1		c.*102G>C		3_prime_UTR	Exon 2 of 2	ENSP00000610622.1
	KCNJ4	ENST00000947103.1		c.*102G>C		3_prime_UTR	Exon 2 of 2	ENSP00000617162.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1260148 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 620298

African (AFR) AF: 0.00 AC: 0 AN: 28124

American (AMR) AF: 0.00 AC: 0 AN: 28754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19242

East Asian (EAS) AF: 0.00 AC: 0 AN: 38130

South Asian (SAS) AF: 0.00 AC: 0 AN: 67320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4002

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 973326

Other (OTH) AF: 0.00 AC: 0 AN: 52624

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 3391

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.64
PhyloP100		-3.4

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: rs1063134; hg19: chr22-38822698;