1-160041410-G-C

Position:

• chr1-160041410-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002241.5(KCNJ10):​c.1123C>G​(p.Arg375Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,576 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R375C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KCNJ10 NM_002241.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11

Genes affected

KCNJ10 (HGNC:6256): (potassium inwardly rectifying channel subfamily J member 10) This gene encodes a member of the inward rectifier-type potassium channel family, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes. [provided by RefSeq, Jul 2008]

KCNJ10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ10	NM_002241.5	c.1123C>G	p.Arg375Gly	missense_variant	2/2	ENST00000644903.1	NP_002232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ10	ENST00000644903.1	c.1123C>G	p.Arg375Gly	missense_variant	2/2		NM_002241.5	ENSP00000495557.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460576 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726568

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000178 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;.;.;D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Uncertain	0.0088	D
MutationAssessor	Uncertain	2.2	M;M;M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.070	.;N;.;.
REVEL	Uncertain	0.52
Sift	Uncertain	0.0030	.;D;.;.
Sift4G	Uncertain	0.046	.;D;.;.
Polyphen		0.99	D;D;D;D
Vest4		0.37
MutPred		0.30		Loss of MoRF binding (P = 3e-04);Loss of MoRF binding (P = 3e-04);Loss of MoRF binding (P = 3e-04);Loss of MoRF binding (P = 3e-04);
MVP		0.82
MPC		0.98
ClinPred		0.85	D
GERP RS		4.8
Varity_R		0.17
gMVP		0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs751338154; hg19: chr1-160011200;