Variant 14-36680661-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_030631.4(SLC25A21):c.897G>T(p.Trp299Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00531 in 1,612,392 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.027 ( 172 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 182 hom. )

Consequence

SLC25A21
NM_030631.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.33

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030671954).

BP6

Variant 14-36680661-C-A is Benign according to our data. Variant chr14-36680661-C-A is described in ClinVar as [Benign]. Clinvar id is 1635468.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A21	NM_030631.4 linkuse as main transcript	c.897G>T	p.Trp299Cys	missense_variant	10/10	ENST00000331299.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A21	ENST00000331299.6 linkuse as main transcript	c.897G>T	p.Trp299Cys	missense_variant	10/10	1	NM_030631.4	P4	Q9BQT8-1
SLC25A21	ENST00000555449.5 linkuse as main transcript	c.896+1G>T		splice_donor_variant		2		A1	Q9BQT8-2

Frequencies

GnomAD3 genomes

AF:

0.0267

AC:

4056

AN:

152086

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0907

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.0181

GnomAD3 exomes

AF:

0.00713

AC:

1778

AN:

249510

Hom.:

AF XY:

0.00546

AC XY:

736

AN XY:

134898

show subpopulations

Gnomad AFR exome

AF:

0.0904

Gnomad AMR exome

AF:

0.00454

Gnomad ASJ exome

AF:

0.00725

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000991

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000566

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00308

AC:

4493

AN:

1460188

Hom.:

182

Cov.:

AF XY:

0.00280

AC XY:

2031

AN XY:

726300

show subpopulations

Gnomad4 AFR exome

AF:

0.0972

Gnomad4 AMR exome

AF:

0.00551

Gnomad4 ASJ exome

AF:

0.00881

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000140

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000293

Gnomad4 OTH exome

AF:

0.00638

GnomAD4 genome

AF:

0.0267

AC:

4065

AN:

152204

Hom.:

172

Cov.:

AF XY:

0.0260

AC XY:

1932

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0907

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00476

Hom.:

Bravo

AF:

0.0303

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0835

AC:

368

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00874

AC:

1061

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000982

EpiControl

AF:

0.000892

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.28

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.36

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.56

MutPred

0.19

Loss of catalytic residue at W299 (P = 0.0515);

MVP

0.85

MPC

0.70

ClinPred

0.037

GERP RS

6.2

Varity_R

0.31

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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