chr14-36976626-G-C

Variant names:

• chr14-36976626-G-C
• rs10483481
• NM_030631.4:c.71-101622C>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.71-101622C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,944 control chromosomes in the GnomAD database, including 18,014 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 0.46 (18014 hom., cov: 31)
• Consequence: SLC25A21 NM_030631.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• 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: AR, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030631.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A21	NM_030631.4	MANE Select	c.71-101622C>G		intron	N/A	NP_085134.1	Q9BQT8-1
	SLC25A21	NM_001171170.2		c.71-101622C>G		intron	N/A	NP_001164641.1	Q9BQT8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A21	ENST00000331299.6	TSL:1 MANE Select	c.71-101622C>G		intron	N/A	ENSP00000329452.5	Q9BQT8-1
	SLC25A21	ENST00000555449.5	TSL:2	c.71-101622C>G		intron	N/A	ENSP00000451873.1	Q9BQT8-2
	SLC25A21	ENST00000557611.1	TSL:5	n.67-101622C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70377 AN: 151826 Hom.: 17965 Cov.: 31

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.464 AC: 70482 AN: 151944 Hom.: 18014 Cov.: 31 AF XY: 0.463 AC XY: 34395 AN XY: 74256

African (AFR) AF: 0.685 AC: 28406 AN: 41444

American (AMR) AF: 0.492 AC: 7514 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1493 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2039 AN: 5140

South Asian (SAS) AF: 0.468 AC: 2254 AN: 4814

European-Finnish (FIN) AF: 0.347 AC: 3665 AN: 10558

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23863 AN: 67932

Other (OTH) AF: 0.436 AC: 919 AN: 2108

Alfa AF: 0.416 Hom.: 1794

Bravo AF: 0.483

Asia WGS AF: 0.445 AC: 1551 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		0.24
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: rs10483481; hg19: chr14-37445831;