14-36858307-C-A

Variant names:

• chr14-36858307-C-A
• rs7144374
• NM_030631.4:c.119+16649G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_030631.4(SLC25A21):​c.119+16649G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,974 control chromosomes in the GnomAD database, including 2,956 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 0.15 (2956 hom., cov: 32)
• Consequence: SLC25A21 NM_030631.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4	c.119+16649G>T		intron_variant	Intron 2 of 9	ENST00000331299.6	NP_085134.1
SLC25A21	NM_001171170.2	c.119+16649G>T		intron_variant	Intron 2 of 10		NP_001164641.1
SLC25A21	XM_047431871.1	c.119+16649G>T		intron_variant	Intron 2 of 8		XP_047287827.1
SLC25A21	XM_011537288.4	c.29+16649G>T		intron_variant	Intron 2 of 9		XP_011535590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A21	ENST00000331299.6	c.119+16649G>T		intron_variant	Intron 2 of 9	1	NM_030631.4	ENSP00000329452.5
SLC25A21	ENST00000555449.5	c.119+16649G>T		intron_variant	Intron 2 of 10	2		ENSP00000451873.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23347 AN: 151856 Hom.: 2948 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0518

Gnomad AMR AF: 0.0704

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.154 AC: 23377 AN: 151974 Hom.: 2956 Cov.: 32 AF XY: 0.152 AC XY: 11282 AN XY: 74274

African (AFR) AF: 0.333 AC: 13806 AN: 41428

American (AMR) AF: 0.0704 AC: 1075 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 331 AN: 3472

East Asian (EAS) AF: 0.256 AC: 1317 AN: 5138

South Asian (SAS) AF: 0.131 AC: 631 AN: 4816

European-Finnish (FIN) AF: 0.106 AC: 1122 AN: 10562

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0696 AC: 4735 AN: 67984

Other (OTH) AF: 0.128 AC: 268 AN: 2100

Alfa AF: 0.0899 Hom.: 1716

Bravo AF: 0.155

Asia WGS AF: 0.191 AC: 662 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		1.0
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: rs7144374; hg19: chr14-37327512;