15-45362129-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001482.3(GATM):​c.1252T>A​(p.Leu418Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L418L) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GATM
NM_001482.3 missense

Scores

3
11
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.29
Variant links:
Genes affected
GATM (HGNC:4175): (glycine amidinotransferase) This gene encodes a mitochondrial enzyme that belongs to the amidinotransferase family. This enzyme is involved in creatine biosynthesis, whereby it catalyzes the transfer of a guanido group from L-arginine to glycine, resulting in guanidinoacetic acid, the immediate precursor of creatine. Mutations in this gene cause arginine:glycine amidinotransferase deficiency, an inborn error of creatine synthesis characterized by cognitive disability, language impairment, and behavioral disorders. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.758

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GATMNM_001482.3 linkuse as main transcriptc.1252T>A p.Leu418Ile missense_variant 9/9 ENST00000396659.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GATMENST00000396659.8 linkuse as main transcriptc.1252T>A p.Leu418Ile missense_variant 9/91 NM_001482.3 P1P50440-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.85e-7
AC:
1
AN:
1459824
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726448
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Uncertain
0.081
D
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.48
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.047
D
MetaRNN
Pathogenic
0.76
D
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Pathogenic
3.1
M
MutationTaster
Benign
0.000062
P
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-1.8
N
REVEL
Uncertain
0.32
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.021
D
Polyphen
0.96
D
Vest4
0.55
MutPred
0.60
Loss of disorder (P = 0.1495);
MVP
0.45
MPC
1.7
ClinPred
0.97
D
GERP RS
3.6
Varity_R
0.79
gMVP
0.77

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: rs1145086; hg19: chr15-45654327; API