chr2-42493333-C-A

Variant names:

• chr2-42493333-C-A
• rs748790243
• NM_133329.6:c.169G>T

Variant summary

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

The NM_133329.6(KCNG3):​c.169G>T​(p.Glu57*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000689 in 1,451,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KCNG3 NM_133329.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• Publications: 0 publications found

Genes affected

KCNG3 (HGNC:18306): (potassium voltage-gated channel modifier subfamily G member 3) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily G. This member is a gamma subunit functioning as a modulatory molecule. Alternative splicing results in two transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNG3	NM_133329.6	c.169G>T	p.Glu57*	stop_gained	Exon 1 of 2	ENST00000306078.2	NP_579875.1
KCNG3	NM_172344.3	c.169G>T	p.Glu57*	stop_gained	Exon 1 of 2		NP_758847.1
KCNG3	XR_007069666.1	n.650G>T		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNG3	ENST00000306078.2	c.169G>T	p.Glu57*	stop_gained	Exon 1 of 2	1	NM_133329.6	ENSP00000304127.1
KCNG3	ENST00000394973.4	c.169G>T	p.Glu57*	stop_gained	Exon 1 of 2	1		ENSP00000378424.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451486 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721298

African (AFR) AF: 0.00 AC: 0 AN: 33202

American (AMR) AF: 0.00 AC: 0 AN: 43756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25796

East Asian (EAS) AF: 0.00 AC: 0 AN: 39290

South Asian (SAS) AF: 0.00 AC: 0 AN: 85012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107382

Other (OTH) AF: 0.00 AC: 0 AN: 59942

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	41
DANN	Uncertain	1.0
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.94	D
PhyloP100		5.8
Vest4		0.26
GERP RS		3.3
Mutation Taster		=13/187	disease causing (fs/PTC)

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: rs748790243; hg19: chr2-42720473;