13-100532344-C-A

Variant summary

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

The NM_001195087.2(GGACT):​c.248G>T​(p.Ser83Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,550,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

GGACT
NM_001195087.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0390
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=0.055998594).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GGACTNM_001195087.2 linkc.248G>T p.Ser83Ile missense_variant Exon 3 of 3 ENST00000683975.1 NP_001182016.1 Q9BVM4
GGACTNM_033110.3 linkc.248G>T p.Ser83Ile missense_variant Exon 2 of 2 NP_149101.1 Q9BVM4
GGACTXM_011521129.4 linkc.248G>T p.Ser83Ile missense_variant Exon 3 of 3 XP_011519431.1 Q9BVM4
GGACTXM_047430708.1 linkc.248G>T p.Ser83Ile 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.248G>T p.Ser83Ile missense_variant Exon 3 of 3 NM_001195087.2 ENSP00000508020.1 Q9BVM4

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000413
Gnomad FIN
AF:
0.000376
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000220
AC:
33
AN:
150232
Hom.:
0
AF XY:
0.000187
AC XY:
15
AN XY:
80304
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000325
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000528
Gnomad FIN exome
AF:
0.000516
Gnomad NFE exome
AF:
0.0000890
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000112
AC:
156
AN:
1398286
Hom.:
0
Cov.:
31
AF XY:
0.000100
AC XY:
69
AN XY:
689706
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000196
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000265
Gnomad4 FIN exome
AF:
0.000452
Gnomad4 NFE exome
AF:
0.0000853
Gnomad4 OTH exome
AF:
0.000224
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152220
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000413
Gnomad4 FIN
AF:
0.000376
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.000132
ExAC
AF:
0.000331
AC:
8

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.248G>T (p.S83I) alteration is located in exon 2 (coding exon 1) of the A2LD1 gene. This alteration results from a G to T substitution at nucleotide position 248, causing the serine (S) at amino acid position 83 to be replaced by an isoleucine (I). 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
Uncertain
0.47
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
15
DANN
Benign
0.96
DEOGEN2
Benign
0.16
T;T
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.80
T;.
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.056
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.9
L;L
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-3.9
D;D
REVEL
Benign
0.18
Sift
Benign
0.059
T;T
Sift4G
Benign
0.074
T;T
Polyphen
0.54
P;P
Vest4
0.16
MVP
0.088
ClinPred
0.10
T
GERP RS
-0.96
Varity_R
0.31
gMVP
0.72

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: rs761731875; hg19: chr13-101184598; API