chr14-36684767-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030631.4(SLC25A21):​c.762G>A​(p.Met254Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M254L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC25A21
NM_030631.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A21NM_030631.4 linkc.762G>A p.Met254Ile 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.762G>A p.Met254Ile missense_variant Exon 8 of 10 1 NM_030631.4 ENSP00000329452.5 Q9BQT8-1
SLC25A21ENST00000555449.5 linkc.762G>A p.Met254Ile missense_variant Exon 8 of 11 2 ENSP00000451873.1 Q9BQT8-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Benign
-0.041
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
17
DANN
Benign
0.64
DEOGEN2
Benign
0.16
.;T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.21
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.52
N;N
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
0.060
N;N
REVEL
Benign
0.22
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
.;B
Vest4
0.39
MutPred
0.52
Loss of phosphorylation at Y258 (P = 0.1481);Loss of phosphorylation at Y258 (P = 0.1481);
MVP
0.49
MPC
0.13
ClinPred
0.34
T
GERP RS
3.7
Varity_R
0.23
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.26
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.26
Position offset: -23

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: rs770189774; hg19: chr14-37153972; API