13-100532402-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001195087.2(GGACT):​c.190G>C​(p.Glu64Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 152,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Consequence

GGACT
NM_001195087.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.782
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06597084).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GGACTNM_001195087.2 linkc.190G>C p.Glu64Gln missense_variant Exon 3 of 3 ENST00000683975.1 NP_001182016.1 Q9BVM4
GGACTNM_033110.3 linkc.190G>C p.Glu64Gln missense_variant Exon 2 of 2 NP_149101.1 Q9BVM4
GGACTXM_011521129.4 linkc.190G>C p.Glu64Gln missense_variant Exon 3 of 3 XP_011519431.1 Q9BVM4
GGACTXM_047430708.1 linkc.190G>C p.Glu64Gln missense_variant Exon 3 of 3 XP_047286664.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GGACTENST00000683975.1 linkc.190G>C p.Glu64Gln missense_variant Exon 3 of 3 NM_001195087.2 ENSP00000508020.1 Q9BVM4

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152242
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152242
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.190G>C (p.E64Q) alteration is located in exon 2 (coding exon 1) of the A2LD1 gene. This alteration results from a G to C substitution at nucleotide position 190, causing the glutamic acid (E) at amino acid position 64 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
3.5
DANN
Benign
0.71
DEOGEN2
Benign
0.0079
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.78
T;.
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.066
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.32
N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.040
N;N
REVEL
Benign
0.037
Sift
Benign
0.32
T;T
Sift4G
Benign
0.43
T;T
Polyphen
0.019
B;B
Vest4
0.053
MutPred
0.33
Gain of catalytic residue at S59 (P = 0.0042);Gain of catalytic residue at S59 (P = 0.0042);
MVP
0.014
ClinPred
0.052
T
GERP RS
-2.3
Varity_R
0.23
gMVP
0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs940222540; hg19: chr13-101184656; API