14-37172557-A-G

Variant names:

• chr14-37172557-A-G
• rs56237223
• NM_030631.4:c.-207T>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_030631.4(SLC25A21):​c.-207T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 712,774 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (26 hom.)
• Consequence: SLC25A21 NM_030631.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.30

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 14-37172557-A-G is Benign according to our data. Variant chr14-37172557-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3777835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4	c.-207T>C		5_prime_UTR_variant	Exon 1 of 10	ENST00000331299.6	NP_085134.1
SLC25A21	NM_001171170.2	c.-207T>C		5_prime_UTR_variant	Exon 1 of 11		NP_001164641.1
SLC25A21	XM_047431871.1	c.-207T>C		5_prime_UTR_variant	Exon 1 of 9		XP_047287827.1
SLC25A21-AS1	NR_033240.1	n.532A>G		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A21	ENST00000331299.6	c.-207T>C		5_prime_UTR_variant	Exon 1 of 10	1	NM_030631.4	ENSP00000329452.5
SLC25A21-AS1	ENST00000556667.1	n.670A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
SLC25A21	ENST00000555449.5	c.-207T>C		upstream_gene_variant		2		ENSP00000451873.1
SLC25A21	ENST00000557611.1	n.-211T>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00531 AC: 808 AN: 152212 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00757

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00395 AC: 547 AN: 138418 Hom.: 5 AF XY: 0.00373 AC XY: 280 AN XY: 75140

Gnomad AFR exome AF: 0.000771

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00285

Gnomad FIN exome AF: 0.0197

Gnomad NFE exome AF: 0.00561

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00570 AC: 3195 AN: 560444 Hom.: 26 Cov.: 5 AF XY: 0.00553 AC XY: 1675 AN XY: 302882

Gnomad4 AFR exome AF: 0.000503

Gnomad4 AMR exome AF: 0.00144

Gnomad4 ASJ exome AF: 0.0000499

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00264

Gnomad4 FIN exome AF: 0.0185

Gnomad4 NFE exome AF: 0.00652

Gnomad4 OTH exome AF: 0.00614

GnomAD4 genome AF: 0.00530 AC: 808 AN: 152330 Hom.: 4 Cov.: 33 AF XY: 0.00534 AC XY: 398 AN XY: 74484

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0211

Gnomad4 NFE AF: 0.00757

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00683 Hom.: 1

Bravo AF: 0.00321

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC25A21-AS1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.081
DANN	Benign	0.32

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

Other links and lift over

dbSNP: rs56237223; hg19: chr14-37641762;