14-36684796-T-A

Variant names:

• chr14-36684796-T-A
• NM_030631.4:c.733A>T

Variant summary

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

The NM_030631.4(SLC25A21):​c.733A>T​(p.Ile245Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A21 NM_030631.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77

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.733A>T	p.Ile245Phe	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.733A>T	p.Ile245Phe	missense_variant	Exon 8 of 10	1	NM_030631.4	ENSP00000329452.5
SLC25A21	ENST00000555449.5	c.733A>T	p.Ile245Phe	missense_variant	Exon 8 of 11	2		ENSP00000451873.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 24, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.733A>T (p.I245F) alteration is located in exon 8 (coding exon 8) of the SLC25A21 gene. This alteration results from a A to T substitution at nucleotide position 733, causing the isoleucine (I) at amino acid position 245 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.49	.;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.026	D;D
Sift4G	Benign	0.085	T;T
Polyphen		0.41	.;B
Vest4		0.59
MutPred		0.37		Gain of methylation at K246 (P = 0.0452);Gain of methylation at K246 (P = 0.0452);
MVP		0.80
MPC		0.69
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.79
gMVP		0.78

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-37154001;