14-36684751-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_030631.4(SLC25A21):​c.778G>A​(p.Glu260Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E260Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC25A21
NM_030631.4 missense

Scores

8
9
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.41
Variant links:
Genes affected
SLC25A21 (HGNC:14411): (solute carrier family 25 member 21) SLC25A21 is a homolog of the S. cerevisiae ODC proteins, mitochondrial carriers that transport C5-C7 oxodicarboxylates across inner mitochondrial membranes. One of the species transported by ODC is 2-oxoadipate, a common intermediate in the catabolism of lysine, tryptophan, and hydroxylysine in mammals. Within mitochondria, 2-oxoadipate is converted into acetyl-CoA.[supplied by OMIM, Apr 2004]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A21NM_030631.4 linkc.778G>A p.Glu260Lys missense_variant Exon 8 of 10 ENST00000331299.6 NP_085134.1 Q9BQT8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A21ENST00000331299.6 linkc.778G>A p.Glu260Lys missense_variant Exon 8 of 10 1 NM_030631.4 ENSP00000329452.5 Q9BQT8-1
SLC25A21ENST00000555449.5 linkc.778G>A p.Glu260Lys missense_variant Exon 8 of 11 2 ENSP00000451873.1 Q9BQT8-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1452748
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
722224
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:
9.02e-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
Uncertain
0.51
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.27
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
.;D
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.90
D;D
MetaSVM
Uncertain
0.41
D
MutationAssessor
Benign
1.8
L;L
PrimateAI
Uncertain
0.48
T
PROVEAN
Uncertain
-3.2
D;D
REVEL
Pathogenic
0.82
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.0090
D;D
Polyphen
1.0
.;D
Vest4
0.81
MutPred
0.71
Gain of methylation at E260 (P = 0.012);Gain of methylation at E260 (P = 0.012);
MVP
0.96
MPC
0.55
ClinPred
0.97
D
GERP RS
5.7
Varity_R
0.77
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr14-37153956; COSMIC: COSV58717654; API