Genetic Variant GGACT:p.Asp135Asn (chr13-100532189-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001195087.2(GGACT):c.403G>A(p.Asp135Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000531 in 1,318,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000053 ( 0 hom. )

Consequence

GGACT
NM_001195087.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

Publications

0 publications found

Variant links:

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]

GGACT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08409363).

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>A	p.Asp135Asn	missense	Exon 3 of 3	NP_001182016.1	Q9BVM4
	GGACT	NM_033110.3		c.403G>A	p.Asp135Asn	missense	Exon 2 of 2	NP_149101.1	Q9BVM4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GGACT	ENST00000683975.1	MANE Select	c.403G>A	p.Asp135Asn	missense	Exon 3 of 3	ENSP00000508020.1	Q9BVM4
GGACT	ENST00000455100.2	TSL:1	c.403G>A	p.Asp135Asn	missense	Exon 2 of 2	ENSP00000410449.1	Q9BVM4
GGACT	ENST00000376250.6	TSL:3	c.403G>A	p.Asp135Asn	missense	Exon 3 of 3	ENSP00000365426.1	Q9BVM4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000108

AC:

AN:

92966

AF XY:

0.00

show subpopulations

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:

0.0000294

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000531

AC:

AN:

1318504

Hom.:

Cov.:

AF XY:

0.00000313

AC XY:

AN XY:

639920

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29414

American (AMR)

AF:

0.00

AC:

AN:

25280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19862

East Asian (EAS)

AF:

0.00

AC:

AN:

34838

South Asian (SAS)

AF:

0.00

AC:

AN:

67532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5286

European-Non Finnish (NFE)

AF:

0.00000675

AC:

AN:

1036380

Other (OTH)

AF:

0.00

AC:

AN:

54328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.71

M_CAP

Benign

0.018

MetaRNN

Benign

0.084

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

1.2

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.12

Sift

Benign

0.11

Sift4G

Benign

0.16

Polyphen

0.014

Vest4

0.085

MutPred

0.26

Gain of catalytic residue at Y137 (P = 0.0065)

MVP

0.055

ClinPred

0.17

GERP RS

4.1

Varity_R

0.23

gMVP

0.37

Mutation Taster

=84/16

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over