NM_030631.4:c.204-7788A>G

Variant names:

• chr14-36742361-T-C
• rs1033594
• NM_030631.4:c.204-7788A>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.204-7788A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,998 control chromosomes in the GnomAD database, including 26,028 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 0.57 (26028 hom., cov: 32)
• Consequence: SLC25A21 NM_030631.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4	c.204-7788A>G		intron_variant	Intron 3 of 9	ENST00000331299.6	NP_085134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A21	ENST00000331299.6	c.204-7788A>G		intron_variant	Intron 3 of 9	1	NM_030631.4	ENSP00000329452.5
SLC25A21	ENST00000555449.5	c.204-7788A>G		intron_variant	Intron 3 of 10	2		ENSP00000451873.1
SLC25A21	ENST00000546428.2	n.70-7788A>G		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86484 AN: 151880 Hom.: 25983 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.570 AC: 86587 AN: 151998 Hom.: 26028 Cov.: 32 AF XY: 0.566 AC XY: 42051 AN XY: 74298

African (AFR) AF: 0.772 AC: 32011 AN: 41472

American (AMR) AF: 0.461 AC: 7026 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1637 AN: 3466

East Asian (EAS) AF: 0.387 AC: 2001 AN: 5174

South Asian (SAS) AF: 0.612 AC: 2947 AN: 4818

European-Finnish (FIN) AF: 0.483 AC: 5092 AN: 10550

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34137 AN: 67946

Other (OTH) AF: 0.537 AC: 1136 AN: 2114

Alfa AF: 0.519 Hom.: 33636

Bravo AF: 0.570

Asia WGS AF: 0.487 AC: 1694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.9
DANN	Benign	0.45
PhyloP100		0.34
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: rs1033594; hg19: chr14-37211566;