rs1566526303

Variant names:

• chr13-100532189-C-A
• rs1566526303
• NM_001195087.2:c.403G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-100532189-C-A
• chr13-100532189-C-T

Variant summary

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

The NM_001195087.2(GGACT):​c.403G>T​(p.Asp135Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. D135N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GGACT NM_001195087.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• 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=0.2738661).

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.403G>T	p.Asp135Tyr	missense	Exon 3 of 3	NP_001182016.1	Q9BVM4
	GGACT	NM_033110.3		c.403G>T	p.Asp135Tyr	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.403G>T	p.Asp135Tyr	missense	Exon 3 of 3	ENSP00000508020.1	Q9BVM4
	GGACT	ENST00000455100.2	TSL:1	c.403G>T	p.Asp135Tyr	missense	Exon 2 of 2	ENSP00000410449.1	Q9BVM4
	GGACT	ENST00000376250.6	TSL:3	c.403G>T	p.Asp135Tyr	missense	Exon 3 of 3	ENSP00000365426.1	Q9BVM4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.0051
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.2
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.30		Gain of catalytic residue at E140 (P = 0.0054)
MVP		0.23
ClinPred		0.91	D
GERP RS		4.1
Varity_R		0.34
gMVP		0.62
Mutation Taster		=79/21	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: rs1566526303; hg19: chr13-101184443;