chr14-36684767-C-T

Variant names:

• chr14-36684767-C-T
• rs770189774
• NM_030631.4:c.762G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030631.4(SLC25A21):​c.762G>A​(p.Met254Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M254L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A21 NM_030631.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A21	NM_030631.4	c.762G>A	p.Met254Ile	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.762G>A	p.Met254Ile	missense_variant	Exon 8 of 10	1	NM_030631.4	ENSP00000329452.5
SLC25A21	ENST00000555449.5	c.762G>A	p.Met254Ile	missense_variant	Exon 8 of 11	2		ENSP00000451873.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.64
DEOGEN2	Benign	0.16	.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.52	N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.060	N;N
REVEL	Benign	0.22
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	.;B
Vest4		0.39
MutPred		0.52		Loss of phosphorylation at Y258 (P = 0.1481);Loss of phosphorylation at Y258 (P = 0.1481);
MVP		0.49
MPC		0.13
ClinPred		0.34	T
GERP RS		3.7
Varity_R		0.23
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.26		Position offset: -23

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

Publications

LitVar

Other links and lift over

dbSNP: rs770189774; hg19: chr14-37153972;