NM_000387.6:c.899A>G

Variant names:

• chr3-48857717-T-C
• rs2083590517
• NM_000387.6:c.899A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_000387.6(SLC25A20):​c.899A>G​(p.Asn300Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: 2.49
• 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 2 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
• BP4: Computational evidence support a benign effect (MetaRNN=0.1801422).

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.899A>G	p.Asn300Ser	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.899A>G	p.Asn300Ser	missense	Exon 9 of 9	ENSP00000326305.4	O43772
	SLC25A20	ENST00000880877.1		c.893A>G	p.Asn298Ser	missense	Exon 9 of 9	ENSP00000550936.1
	SLC25A20	ENST00000880878.1		c.716A>G	p.Asn239Ser	missense	Exon 7 of 7	ENSP00000550937.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000756

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	0.069
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.091
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.5
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.25
Sift	Benign	0.16	T
Sift4G	Benign	0.42	T
Polyphen		0.032	B
Vest4		0.13
MVP		0.87
MPC		0.21
ClinPred		0.32	T
GERP RS		5.7
Varity_R		0.038
gMVP		0.76
Mutation Taster		=81/19	polymorphism

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

dbSNP: rs2083590517; hg19: chr3-48895150;