18-12348286-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006796.3(AFG3L2):​c.1650A>C​(p.Glu550Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. E550E) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

AFG3L2
NM_006796.3 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.278
Variant links:
Genes affected
AFG3L2 (HGNC:315): (AFG3 like matrix AAA peptidase subunit 2) This gene encodes a protein localized in mitochondria and closely related to paraplegin. The paraplegin gene is responsible for an autosomal recessive form of hereditary spastic paraplegia. This gene is a candidate gene for other hereditary spastic paraplegias or neurodegenerative disorders. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32670963).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AFG3L2NM_006796.3 linkc.1650A>C p.Glu550Asp missense_variant Exon 13 of 17 ENST00000269143.8 NP_006787.2 Q9Y4W6Q8TA92
AFG3L2XM_011525601.4 linkc.1650A>C p.Glu550Asp missense_variant Exon 13 of 16 XP_011523903.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AFG3L2ENST00000269143.8 linkc.1650A>C p.Glu550Asp missense_variant Exon 13 of 17 1 NM_006796.3 ENSP00000269143.2 Q9Y4W6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461326
Hom.:
0
Cov.:
38
AF XY:
0.00000138
AC XY:
1
AN XY:
727006
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.82
BayesDel_addAF
Uncertain
0.032
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
11
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.70
D
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.90
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.054
D
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
0.51
N
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-2.6
D
REVEL
Uncertain
0.52
Sift
Uncertain
0.018
D
Sift4G
Benign
0.27
T
Polyphen
0.33
B
Vest4
0.34
MutPred
0.55
Loss of helix (P = 0.1299);
MVP
0.61
MPC
1.1
ClinPred
0.85
D
GERP RS
-1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.59
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-12348285; API