21-38299349-A-G

Variant names:

• chr21-38299349-A-G
• rs3746875
• NM_170736.3:c.88A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170736.3(KCNJ15):​c.88A>G​(p.Met30Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,876 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KCNJ15 NM_170736.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00
• Publications: 0 publications found

Genes affected

KCNJ15 (HGNC:6261): (potassium inwardly rectifying channel subfamily J member 15) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14184317).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170736.3. 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
	KCNJ15	NM_170736.3	MANE Select	c.88A>G	p.Met30Val	missense	Exon 3 of 3	NP_733932.1	Q99712
	KCNJ15	NM_001276435.2		c.88A>G	p.Met30Val	missense	Exon 5 of 5	NP_001263364.1	Q99712
	KCNJ15	NM_001276436.2		c.88A>G	p.Met30Val	missense	Exon 5 of 5	NP_001263365.1	Q99712

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ15	ENST00000398938.7	TSL:1 MANE Select	c.88A>G	p.Met30Val	missense	Exon 3 of 3	ENSP00000381911.2	Q99712
	KCNJ15	ENST00000328656.8	TSL:1	c.88A>G	p.Met30Val	missense	Exon 4 of 4	ENSP00000331698.3	Q99712
	KCNJ15	ENST00000398930.5	TSL:5	c.88A>G	p.Met30Val	missense	Exon 4 of 4	ENSP00000381904.1	Q99712

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

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: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111996

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Benign	0.45
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	-0.99	N
PhyloP100		5.0
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.40
Sift	Uncertain	0.015	D
Sift4G	Benign	0.063	T
Polyphen		0.0050	B
Vest4		0.15
MutPred		0.37		Loss of catalytic residue at M30 (P = 0.057)
MVP		0.78
MPC		0.45
ClinPred		0.56	D
GERP RS		5.1
Varity_R		0.26
gMVP		0.56
Mutation Taster		=90/10	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: rs3746875; hg19: chr21-39671271;