chr15-45402535-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_024063.3(AFG2B):​c.106C>T​(p.Leu36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,597,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AFG2B
NM_024063.3 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.167
Variant links:
Genes affected
AFG2B (HGNC:28762): (AFG2 AAA ATPase homolog B) Predicted to enable ATP binding activity. Located in cytoplasm and spindle. [provided by Alliance of Genome Resources, Apr 2022]
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 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=0.08883786).
BP6
Variant 15-45402535-C-T is Benign according to our data. Variant chr15-45402535-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3840470.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AFG2BNM_024063.3 linkc.106C>T p.Leu36Phe missense_variant Exon 1 of 8 ENST00000305560.11 NP_076968.2 Q9BVQ7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPATA5L1ENST00000305560.11 linkc.106C>T p.Leu36Phe missense_variant Exon 1 of 8 1 NM_024063.3 ENSP00000305494.6 Q9BVQ7-1
SPATA5L1ENST00000531970.5 linkn.106C>T non_coding_transcript_exon_variant Exon 1 of 8 2 ENSP00000436823.1 Q9BVQ7-2
SPATA5L1ENST00000559860.2 linkn.166C>T non_coding_transcript_exon_variant Exon 1 of 5 2
GATMENST00000458245.5 linkn.-208G>A upstream_gene_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152240
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
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
AF:
6.92e-7
AC:
1
AN:
1445204
Hom.:
0
Cov.:
33
AF XY:
0.00000139
AC XY:
1
AN XY:
717990
show subpopulations
Gnomad4 AFR exome
AF:
0.0000304
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152240
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.0000482
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
Bravo
AF:
0.00000378
ExAC
AF:
0.00000836
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Jan 31, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.095
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
5.5
DANN
Uncertain
0.98
DEOGEN2
Benign
0.020
T;.
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.60
T;T
M_CAP
Benign
0.055
D
MetaRNN
Benign
0.089
T;T
MetaSVM
Benign
-0.44
T
MutationAssessor
Benign
0.30
N;N
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-2.0
N;.
REVEL
Benign
0.23
Sift
Benign
0.14
T;.
Sift4G
Benign
0.088
T;.
Polyphen
0.0
B;.
Vest4
0.040
MutPred
0.52
Loss of disorder (P = 0.0778);Loss of disorder (P = 0.0778);
MVP
0.78
MPC
1.0
ClinPred
0.11
T
GERP RS
0.59
Varity_R
0.087
gMVP
0.67

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: rs759300414; hg19: chr15-45694733; API