14-36684751-C-T

Variant names:

• chr14-36684751-C-T
• NM_030631.4:c.778G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030631.4(SLC25A21):​c.778G>A​(p.Glu260Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E260Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC25A21 NM_030631.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.41

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4	c.778G>A	p.Glu260Lys	missense_variant	Exon 8 of 10	ENST00000331299.6	NP_085134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A21	ENST00000331299.6	c.778G>A	p.Glu260Lys	missense_variant	Exon 8 of 10	1	NM_030631.4	ENSP00000329452.5
SLC25A21	ENST00000555449.5	c.778G>A	p.Glu260Lys	missense_variant	Exon 8 of 11	2		ENSP00000451873.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452748 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	.;D
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	.;D
Vest4		0.81
MutPred		0.71		Gain of methylation at E260 (P = 0.012);Gain of methylation at E260 (P = 0.012);
MVP		0.96
MPC		0.55
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.77
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-37153956; COSMIC: COSV58717654;