3-48857748-C-G

Variant names:

• chr3-48857748-C-G
• NM_000387.6:c.868G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_000387.6(SLC25A20):​c.868G>C​(p.Ala290Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A290T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A20 NM_000387.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88
• Publications: 0 publications found

Genes affected

SLC25A20 (HGNC:1421): (solute carrier family 25 member 20) This gene product is one of several closely related mitochondrial-membrane carrier proteins that shuttle substrates between cytosol and the intramitochondrial matrix space. This protein mediates the transport of acylcarnitines into mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. Mutations in this gene are associated with carnitine-acylcarnitine translocase deficiency, which can cause a variety of pathological conditions such as hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and is usually lethal in new born and infants. [provided by RefSeq, Jul 2008]

PRKAR2A-AS1 (HGNC:40471): (PRKAR2A antisense RNA 1)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM1: In a repeat Solcar 3 (size 86) in uniprot entity MCAT_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in NM_000387.6
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.846

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A20	NM_000387.6	c.868G>C	p.Ala290Pro	missense_variant	Exon 9 of 9	ENST00000319017.5	NP_000378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A20	ENST00000319017.5	c.868G>C	p.Ala290Pro	missense_variant	Exon 9 of 9	1	NM_000387.6	ENSP00000326305.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Apr 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.868G>C (p.A290P) alteration is located in exon 9 (coding exon 9) of the SLC25A20 gene. This alteration results from a G to C substitution at nucleotide position 868, causing the alanine (A) at amino acid position 290 to be replaced by a proline (P). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	.;D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.8	.;M
PhyloP100		7.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.26	B;B
Vest4		0.85
MutPred		0.72		.;Gain of methylation at K292 (P = 0.0893);
MVP		0.95
MPC		0.44
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.99
gMVP		0.97
Mutation Taster		=21/79	disease causing

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

hg19: chr3-48895181;