NM_030631.4:c.70+109584C>T

Variant names:

• chr14-37062697-G-A
• rs1956424
• NM_030631.4:c.70+109584C>T

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+109584C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,084 control chromosomes in the GnomAD database, including 8,268 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 0.22 (8268 hom., cov: 32)
• Consequence: SLC25A21 NM_030631.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4	c.70+109584C>T		intron_variant	Intron 1 of 9	ENST00000331299.6	NP_085134.1
SLC25A21	NM_001171170.2	c.70+109584C>T		intron_variant	Intron 1 of 10		NP_001164641.1
SLC25A21	XM_047431871.1	c.70+109584C>T		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+109584C>T		intron_variant	Intron 1 of 9	1	NM_030631.4	ENSP00000329452.5
SLC25A21	ENST00000555449.5	c.70+109584C>T		intron_variant	Intron 1 of 10	2		ENSP00000451873.1
SLC25A21	ENST00000557611.1	n.66+109584C>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32946 AN: 151966 Hom.: 8237 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.0568

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.217 AC: 33025 AN: 152084 Hom.: 8268 Cov.: 32 AF XY: 0.211 AC XY: 15695 AN XY: 74346

African (AFR) AF: 0.611 AC: 25339 AN: 41454

American (AMR) AF: 0.123 AC: 1873 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 297 AN: 3472

East Asian (EAS) AF: 0.260 AC: 1339 AN: 5142

South Asian (SAS) AF: 0.0560 AC: 270 AN: 4822

European-Finnish (FIN) AF: 0.0279 AC: 296 AN: 10602

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0470 AC: 3198 AN: 68002

Other (OTH) AF: 0.175 AC: 370 AN: 2114

Alfa AF: 0.0969 Hom.: 10164

Bravo AF: 0.243

Asia WGS AF: 0.159 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.40
PhyloP100		-0.047
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1956424; hg19: chr14-37531902;