14-37172560-G-T

Variant names:

• chr14-37172560-G-T
• rs45449092
• NM_030631.4:c.-210C>A

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.-210C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 710,320 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (18 hom., cov: 33)
  • Exomes 𝑓: 0.011 (56 hom.)
• Consequence: SLC25A21 NM_030631.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.318

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=-0.77).
• BP6: Variant 14-37172560-G-T is Benign according to our data. Variant chr14-37172560-G-T is described in ClinVar as [Benign]. Clinvar id is 3024861.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4	c.-210C>A		5_prime_UTR_variant	Exon 1 of 10	ENST00000331299.6	NP_085134.1
SLC25A21	NM_001171170.2	c.-210C>A		5_prime_UTR_variant	Exon 1 of 11		NP_001164641.1
SLC25A21	XM_047431871.1	c.-210C>A		5_prime_UTR_variant	Exon 1 of 9		XP_047287827.1
SLC25A21-AS1	NR_033240.1	n.535G>T		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.-210C>A		5_prime_UTR_variant	Exon 1 of 10	1	NM_030631.4	ENSP00000329452.5
SLC25A21-AS1	ENST00000556667.1	n.673G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
SLC25A21	ENST00000555449.5	c.-210C>A		upstream_gene_variant		2		ENSP00000451873.1
SLC25A21	ENST00000557611.1	n.-214C>A		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1599 AN: 152228 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00942

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00860 AC: 1189 AN: 138220 Hom.: 14 AF XY: 0.00825 AC XY: 619 AN XY: 75044

Gnomad AFR exome AF: 0.00216

Gnomad AMR exome AF: 0.00690

Gnomad ASJ exome AF: 0.00156

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00165

Gnomad FIN exome AF: 0.0494

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.0144

GnomAD4 exome AF: 0.0106 AC: 5901 AN: 557974 Hom.: 56 Cov.: 5 AF XY: 0.00986 AC XY: 2974 AN XY: 301568

Gnomad4 AFR exome AF: 0.00189

Gnomad4 AMR exome AF: 0.00676

Gnomad4 ASJ exome AF: 0.00165

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00176

Gnomad4 FIN exome AF: 0.0442

Gnomad4 NFE exome AF: 0.0111

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0105 AC: 1598 AN: 152346 Hom.: 18 Cov.: 33 AF XY: 0.0122 AC XY: 912 AN XY: 74490

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00941

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.00694 Hom.: 1

Bravo AF: 0.00722

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC25A21-AS1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.7
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs45449092; hg19: chr14-37641765;