13-100532402-C-A

Variant names:

• chr13-100532402-C-A
• rs940222540
• NM_001195087.2:c.190G>T

Variant summary

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

The NM_001195087.2(GGACT):​c.190G>T​(p.Glu64*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,902 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GGACT NM_001195087.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782
• Publications: 0 publications found

Genes affected

GGACT (HGNC:25100): (gamma-glutamylamine cyclotransferase) The protein encoded by this gene aids in the proteolytic degradation of crosslinked fibrin by breaking down isodipeptide L-gamma-glutamyl-L-epsilon-lysine, a byproduct of fibrin degradation. The reaction catalyzed by the encoded gamma-glutamylaminecyclotransferase produces 5-oxo-L-proline and a free alkylamine. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Aug 2010]

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_001195087.2. 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
	GGACT	NM_001195087.2	MANE Select	c.190G>T	p.Glu64*	stop_gained	Exon 3 of 3	NP_001182016.1	Q9BVM4
	GGACT	NM_033110.3		c.190G>T	p.Glu64*	stop_gained	Exon 2 of 2	NP_149101.1	Q9BVM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGACT	ENST00000683975.1	MANE Select	c.190G>T	p.Glu64*	stop_gained	Exon 3 of 3	ENSP00000508020.1	Q9BVM4
	GGACT	ENST00000455100.2	TSL:1	c.190G>T	p.Glu64*	stop_gained	Exon 2 of 2	ENSP00000410449.1	Q9BVM4
	GGACT	ENST00000376250.6	TSL:3	c.190G>T	p.Glu64*	stop_gained	Exon 3 of 3	ENSP00000365426.1	Q9BVM4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000679 AC: 1 AN: 147202 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000184

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397902 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689530

African (AFR) AF: 0.00 AC: 0 AN: 31578

American (AMR) AF: 0.00 AC: 0 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25150

East Asian (EAS) AF: 0.00 AC: 0 AN: 35724

South Asian (SAS) AF: 0.00 AC: 0 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078630

Other (OTH) AF: 0.00 AC: 0 AN: 57952

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	28
DANN	Uncertain	0.98
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.052	N
PhyloP100		-0.78
Vest4		0.089
GERP RS		-2.3
Mutation Taster		=28/172	disease causing

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: rs940222540; hg19: chr13-101184656;