Genetic Variant SLC25A20:p.Gln4Glu (chr3-48898785-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_000387.6(SLC25A20):c.10C>G(p.Gln4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000422 in 1,421,010 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 1 hom. )

Consequence

SLC25A20
NM_000387.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.440

Publications

3 publications found

Variant links:

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]

SLC25A20 Gene-Disease associations (from GenCC):

carnitine-acylcarnitine translocase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Orphanet, Ambry Genetics, G2P

SLC25A20 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM1

In a chain Mitochondrial carnitine/acylcarnitine carrier protein (size 299) in uniprot entity MCAT_HUMAN there are 10 pathogenic changes around while only 2 benign (83%) in NM_000387.6

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050506502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A20	NM_000387.6 link	c.10C>G	p.Gln4Glu	missense_variant	Exon 1 of 9	ENST00000319017.5	NP_000378.1	O43772

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC25A20	ENST00000319017.5 link	c.10C>G	p.Gln4Glu	missense_variant	Exon 1 of 9	1	NM_000387.6	ENSP00000326305.4	O43772
SLC25A20	ENST00000430379.5 link	c.10C>G	p.Gln4Glu	missense_variant	Exon 1 of 7	3		ENSP00000388986.1	C9JPE1
SLC25A20	ENST00000440964.1 link	n.10C>G		non_coding_transcript_exon_variant	Exon 1 of 10	2		ENSP00000388563.1	F8WEF6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000165

AC:

AN:

181278

AF XY:

0.0000309

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000422

AC:

AN:

1421010

Hom.:

Cov.:

AF XY:

0.00000711

AC XY:

AN XY:

703284

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32506

American (AMR)

AF:

0.00

AC:

AN:

38518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25422

East Asian (EAS)

AF:

0.00

AC:

AN:

37390

South Asian (SAS)

AF:

0.0000740

AC:

AN:

81106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091628

Other (OTH)

AF:

0.00

AC:

AN:

58784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000847

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.6

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.56

.;N

PhyloP100

0.44

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.093

MutPred

0.19

Loss of glycosylation at K6 (P = 0.0284);Loss of glycosylation at K6 (P = 0.0284);

MVP

0.84

MPC

0.29

ClinPred

0.029

GERP RS

-4.2

PromoterAI

0.063

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.052

gMVP

0.42

Mutation Taster

=96/4

polymorphism

(source)

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

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3-48898785-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over