14-37172313-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030631.4(SLC25A21):c.38C>T(p.Ala13Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A13D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC25A21
NM_030631.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

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]

SLC25A21 links:

SLC25A21-AS1 (HGNC:44298): (SLC25A21 antisense RNA 1)

SLC25A21-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24193338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 10	ENST00000331299.6	NP_085134.1	Q9BQT8-1
SLC25A21	NM_001171170.2 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 11		NP_001164641.1	Q9BQT8-2
SLC25A21	XM_047431871.1 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 9		XP_047287827.1
SLC25A21-AS1	NR_033240.1 link	n.288G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC25A21	ENST00000331299.6 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 10	1	NM_030631.4	ENSP00000329452.5	Q9BQT8-1
SLC25A21	ENST00000555449.5 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 11	2		ENSP00000451873.1	Q9BQT8-2
SLC25A21-AS1	ENST00000556667.1 link	n.426G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
SLC25A21	ENST00000557611.1 link	n.34C>T		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000437

AC:

AN:

228966

Hom.:

AF XY:

0.00

AC XY:

AN XY:

123608

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450548

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720254

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000231

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

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Apr 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 13 of the SLC25A21 protein (p.Ala13Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SLC25A21-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

.;T

Eigen

Benign

-0.025

Eigen_PC

Benign

-0.0039

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.52

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.24

Sift

Benign

0.093

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.54

.;P

Vest4

0.45

MutPred

0.45

Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);

MVP

0.87

MPC

0.34

ClinPred

0.83

GERP RS

2.5

Varity_R

0.069

gMVP

0.55

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over