14-36680661-C-A

Variant names:

• chr14-36680661-C-A
• rs17104991
• NM_030631.4:c.897G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001171170.2(SLC25A21):​c.896+1G>T variant causes a splice donor, intron 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (172 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (182 hom.)
• Consequence: SLC25A21 NM_001171170.2 splice_donor, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.33

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]

ACMG classification

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4	c.897G>T	p.Trp299Cys	missense_variant	Exon 10 of 10	ENST00000331299.6	NP_085134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A21	ENST00000331299.6	c.897G>T	p.Trp299Cys	missense_variant	Exon 10 of 10	1	NM_030631.4	ENSP00000329452.5
SLC25A21	ENST00000555449.5	c.896+1G>T		splice_donor_variant, intron_variant	Intron 10 of 10	2		ENSP00000451873.1

Frequencies

GnomAD3 genomes AF: 0.0267 AC: 4056 AN: 152086 Hom.: 173 Cov.: 32

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.: 69 AF XY: 0.00546 AC XY: 736 AN XY: 134898

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.: 31 AF XY: 0.00280 AC XY: 2031 AN XY: 726300

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.: 32 AF XY: 0.0260 AC XY: 1932 AN XY: 74398

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.: 51

Bravo AF: 0.0303

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0835 AC: 368

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.00874 AC: 1061

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000982

EpiControl AF: 0.000892

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.28	N
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.19		Loss of catalytic residue at W299 (P = 0.0515);
MVP		0.85
MPC		0.70
ClinPred		0.037	T
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

Other links and lift over

dbSNP: rs17104991; hg19: chr14-37149866;