rs200226170

Variant names:

• chr12-110453063-C-A
• rs200226170
• NM_016301.4:c.826G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-110453063-C-A
• chr12-110453063-C-T

Variant summary

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

The NM_016301.4(GPN3):​c.826G>T​(p.Glu276*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000754 in 1,326,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: GPN3 NM_016301.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.90
• Publications: 0 publications found

Genes affected

GPN3 (HGNC:30186): (GPN-loop GTPase 3) Predicted to enable GTPase activity. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000300534 (HGNC:):

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016301.4. 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
	GPN3	NM_016301.4	MANE Select	c.826G>T	p.Glu276*	stop_gained	Exon 8 of 8	NP_057385.3
	GPN3	NM_001164372.2		c.943G>T	p.Glu315*	stop_gained	Exon 8 of 8	NP_001157844.1	Q9UHW5-3
	GPN3	NM_001164373.2		c.856G>T	p.Glu286*	stop_gained	Exon 8 of 8	NP_001157845.1	Q9UHW5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPN3	ENST00000228827.8	TSL:1 MANE Select	c.826G>T	p.Glu276*	stop_gained	Exon 8 of 8	ENSP00000228827.3	Q9UHW5-1
	GPN3	ENST00000537466.6	TSL:1	c.856G>T	p.Glu286*	stop_gained	Exon 8 of 8	ENSP00000443068.2	Q9UHW5-2
	GPN3	ENST00000543199.5	TSL:5	c.943G>T	p.Glu315*	stop_gained	Exon 8 of 8	ENSP00000442770.1	Q9UHW5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.54e-7 AC: 1 AN: 1326304 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 666780

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30894

American (AMR) AF: 0.00 AC: 0 AN: 44108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25262

East Asian (EAS) AF: 0.00 AC: 0 AN: 39074

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5488

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 989562

Other (OTH) AF: 0.00 AC: 0 AN: 55920

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Uncertain	0.94	D
PhyloP100		4.9
Vest4		0.31
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=15/185	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs200226170; hg19: chr12-110890868; COSMIC: COSV99959474; COSMIC: COSV99959474;