14-37151549-T-C

Variant names:

• chr14-37151549-T-C
• rs7140725
• NM_030631.4:c.70+20732A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030631.4(SLC25A21):​c.70+20732A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 152,216 control chromosomes in the GnomAD database, including 298 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.044 (298 hom., cov: 32)
• Consequence: SLC25A21 NM_030631.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial DNA depletion syndrome 18

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4	c.70+20732A>G		intron_variant	Intron 1 of 9	ENST00000331299.6	NP_085134.1
SLC25A21	NM_001171170.2	c.70+20732A>G		intron_variant	Intron 1 of 10		NP_001164641.1
SLC25A21	XM_047431871.1	c.70+20732A>G		intron_variant	Intron 1 of 8		XP_047287827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A21	ENST00000331299.6	c.70+20732A>G		intron_variant	Intron 1 of 9	1	NM_030631.4	ENSP00000329452.5
SLC25A21	ENST00000555449.5	c.70+20732A>G		intron_variant	Intron 1 of 10	2		ENSP00000451873.1
SLC25A21	ENST00000557611.1	n.66+20732A>G		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6728 AN: 152098 Hom.: 290 Cov.: 32

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0578

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.00717

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0407

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0444 AC: 6760 AN: 152216 Hom.: 298 Cov.: 32 AF XY: 0.0437 AC XY: 3250 AN XY: 74416

African (AFR) AF: 0.0868 AC: 3606 AN: 41530

American (AMR) AF: 0.102 AC: 1564 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.0585 AC: 303 AN: 5178

South Asian (SAS) AF: 0.00704 AC: 34 AN: 4828

European-Finnish (FIN) AF: 0.00717 AC: 76 AN: 10604

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0158 AC: 1074 AN: 68002

Other (OTH) AF: 0.0412 AC: 87 AN: 2112

Alfa AF: 0.0262 Hom.: 259

Bravo AF: 0.0552

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.81
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7140725; hg19: chr14-37620754;