rs759262977

Variant names:

• chr3-48862652-G-A
• rs759262977
• NM_000387.6:c.425C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-48862652-G-A
• chr3-48862652-G-C

Variant summary

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

The NM_000387.6(SLC25A20):​c.425C>T​(p.Ala142Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 1,456,580 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A142G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: SLC25A20 NM_000387.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.97
• 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.425C>T	p.Ala142Val	missense	Exon 5 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.425C>T	p.Ala142Val	missense	Exon 5 of 9	ENSP00000326305.4	O43772
	SLC25A20	ENST00000880878.1		c.425C>T	p.Ala142Val	missense	Exon 5 of 7	ENSP00000550937.1
	SLC25A20	ENST00000430379.5	TSL:3	c.206C>T	p.Ala69Val	missense	Exon 3 of 7	ENSP00000388986.1	C9JPE1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000687 AC: 10 AN: 1456580 Hom.: 0 Cov.: 29 AF XY: 0.00000966 AC XY: 7 AN XY: 725002

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000903 AC: 10 AN: 1107242

Other (OTH) AF: 0.00 AC: 0 AN: 60166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000113

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.1	L
PhyloP100		10
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.51
Sift	Benign	0.29	T
Sift4G	Benign	0.26	T
Polyphen		0.24	B
Vest4		0.76
MutPred		0.42		Loss of disorder (P = 0.0785)
MVP		0.86
MPC		0.34
ClinPred		0.89	D
GERP RS		5.6
Varity_R		0.67
gMVP		0.56
Mutation Taster		=10/90	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 1

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

Other links and lift over

dbSNP: rs759262977; hg19: chr3-48900085;