Genetic Variant SLC25A21:p.Gly21Asp (chr14-37172289-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

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

The NM_030631.4(SLC25A21):c.62G>A(p.Gly21Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 1,597,360 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. G21A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC25A21
NM_030631.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4 link	c.62G>A	p.Gly21Asp	missense_variant	Exon 1 of 10	ENST00000331299.6	NP_085134.1	Q9BQT8-1
SLC25A21	NM_001171170.2 link	c.62G>A	p.Gly21Asp	missense_variant	Exon 1 of 11		NP_001164641.1	Q9BQT8-2
SLC25A21	XM_047431871.1 link	c.62G>A	p.Gly21Asp	missense_variant	Exon 1 of 9		XP_047287827.1
SLC25A21-AS1	NR_033240.1 link	n.264C>T		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.62G>A	p.Gly21Asp	missense_variant	Exon 1 of 10	1	NM_030631.4	ENSP00000329452.5	Q9BQT8-1
SLC25A21	ENST00000555449.5 link	c.62G>A	p.Gly21Asp	missense_variant	Exon 1 of 11	2		ENSP00000451873.1	Q9BQT8-2
SLC25A21-AS1	ENST00000556667.1 link	n.402C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
SLC25A21	ENST00000557611.1 link	n.58G>A		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000454

AC:

AN:

220258

Hom.:

AF XY:

0.00

AC XY:

AN XY:

118990

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1445114

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717156

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:

0.00000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

.;D

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.39

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

3.9

H;H

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

.;D

Vest4

0.78

MVP

0.95

MPC

0.60

ClinPred

0.99

GERP RS

3.4

Varity_R

0.73

gMVP

0.91

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over