chr13-100532213-C-T

Variant names:

• chr13-100532213-C-T
• rs967601270
• NM_001195087.2:c.379G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001195087.2(GGACT):​c.379G>A​(p.Glu127Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GGACT NM_001195087.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28029978).

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.379G>A	p.Glu127Lys	missense	Exon 3 of 3	NP_001182016.1	Q9BVM4
	GGACT	NM_033110.3		c.379G>A	p.Glu127Lys	missense	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.379G>A	p.Glu127Lys	missense	Exon 3 of 3	ENSP00000508020.1	Q9BVM4
	GGACT	ENST00000455100.2	TSL:1	c.379G>A	p.Glu127Lys	missense	Exon 2 of 2	ENSP00000410449.1	Q9BVM4
	GGACT	ENST00000376250.6	TSL:3	c.379G>A	p.Glu127Lys	missense	Exon 3 of 3	ENSP00000365426.1	Q9BVM4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.0036
Eigen_PC	Benign	-0.0020
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.13
Sift	Benign	0.050	D
Sift4G	Benign	0.15	T
Polyphen		0.80	P
Vest4		0.18
MutPred		0.41		Gain of methylation at E127 (P = 0.0016)
MVP		0.081
ClinPred		0.83	D
GERP RS		4.2
Varity_R		0.51
gMVP		0.48
Mutation Taster		=86/14	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: rs967601270; hg19: chr13-101184467;