3-48857721-G-C

Variant names:

• chr3-48857721-G-C
• rs2083590608
• NM_000387.6:c.895C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000387.6(SLC25A20):​c.895C>G​(p.Pro299Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: SLC25A20 NM_000387.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.94
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a chain Mitochondrial carnitine/acylcarnitine carrier protein (size 299) in uniprot entity MCAT_HUMAN there are 13 pathogenic changes around while only 2 benign (87%) in NM_000387.6
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000387.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A20	NM_000387.6	MANE Select	c.895C>G	p.Pro299Ala	missense	Exon 9 of 9	NP_000378.1	O43772

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A20	ENST00000319017.5	TSL:1 MANE Select	c.895C>G	p.Pro299Ala	missense	Exon 9 of 9	ENSP00000326305.4	O43772
	SLC25A20	ENST00000880877.1		c.889C>G	p.Pro297Ala	missense	Exon 9 of 9	ENSP00000550936.1
	SLC25A20	ENST00000880878.1		c.712C>G	p.Pro238Ala	missense	Exon 7 of 7	ENSP00000550937.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461690 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727140

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111932

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Carnitine acylcarnitine translocase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	T
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.9
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.36		Loss of glycosylation at T298 (P = 0.0359)
MVP		0.97
MPC		0.34
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.17
gMVP		0.89
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2083590608; hg19: chr3-48895154;