14-36851009-C-T

Variant names:

• chr14-36851009-C-T
• rs382321
• NM_030631.4:c.119+23947G>A

Variant summary

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

The NM_030631.4(SLC25A21):​c.119+23947G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,032 control chromosomes in the GnomAD database, including 7,439 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 0.31 (7439 hom., cov: 32)
• Consequence: SLC25A21 NM_030631.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• Publications: 4 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

LOC107984668 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4	c.119+23947G>A		intron_variant	Intron 2 of 9	ENST00000331299.6	NP_085134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A21	ENST00000331299.6	c.119+23947G>A		intron_variant	Intron 2 of 9	1	NM_030631.4	ENSP00000329452.5
SLC25A21	ENST00000555449.5	c.119+23947G>A		intron_variant	Intron 2 of 10	2		ENSP00000451873.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46728 AN: 151914 Hom.: 7423 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.308 AC: 46773 AN: 152032 Hom.: 7439 Cov.: 32 AF XY: 0.309 AC XY: 22939 AN XY: 74322

African (AFR) AF: 0.382 AC: 15829 AN: 41462

American (AMR) AF: 0.302 AC: 4616 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3472

East Asian (EAS) AF: 0.313 AC: 1620 AN: 5174

South Asian (SAS) AF: 0.273 AC: 1314 AN: 4814

European-Finnish (FIN) AF: 0.301 AC: 3176 AN: 10558

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18137 AN: 67958

Other (OTH) AF: 0.306 AC: 646 AN: 2112

Alfa AF: 0.278 Hom.: 25014

Bravo AF: 0.312

Asia WGS AF: 0.311 AC: 1081 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	2.1
DANN	Benign	0.32
PhyloP100		0.18
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: rs382321; hg19: chr14-37320214;