Genetic Variant SLC25A21:p.Val7Ile (chr14-37172332-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030631.4(SLC25A21):c.19G>A(p.Val7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC25A21
NM_030631.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058885068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4 link	c.19G>A	p.Val7Ile	missense_variant	Exon 1 of 10	ENST00000331299.6	NP_085134.1	Q9BQT8-1
SLC25A21	NM_001171170.2 link	c.19G>A	p.Val7Ile	missense_variant	Exon 1 of 11		NP_001164641.1	Q9BQT8-2
SLC25A21	XM_047431871.1 link	c.19G>A	p.Val7Ile	missense_variant	Exon 1 of 9		XP_047287827.1
SLC25A21-AS1	NR_033240.1 link	n.307C>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.19G>A	p.Val7Ile	missense_variant	Exon 1 of 10	1	NM_030631.4	ENSP00000329452.5	Q9BQT8-1
SLC25A21	ENST00000555449.5 link	c.19G>A	p.Val7Ile	missense_variant	Exon 1 of 11	2		ENSP00000451873.1	Q9BQT8-2
SLC25A21-AS1	ENST00000556667.1 link	n.445C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
SLC25A21	ENST00000557611.1 link	n.15G>A		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000437

AC:

AN:

228730

Hom.:

AF XY:

0.00

AC XY:

AN XY:

123432

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:

0.0000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450448

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720214

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:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19G>A (p.V7I) alteration is located in exon 1 (coding exon 1) of the SLC25A21 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the valine (V) at amino acid position 7 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.17

.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

-0.34

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.13

Sift

Benign

0.71

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0

.;B

Vest4

0.11

MutPred

0.18

Gain of methylation at K4 (P = 0.1218);Gain of methylation at K4 (P = 0.1218);

MVP

0.33

MPC

0.095

ClinPred

0.053

GERP RS

3.4

Varity_R

0.038

gMVP

0.23

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