Variant rs759262977 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

SLC25A20
NM_000387.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.97

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A20	NM_000387.6 linkuse as main transcript	c.425C>T	p.Ala142Val	missense_variant	5/9	ENST00000319017.5	NP_000378.1	O43772

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC25A20	ENST00000319017.5 linkuse as main transcript	c.425C>T	p.Ala142Val	missense_variant	5/9	1	NM_000387.6	ENSP00000326305.4	O43772
SLC25A20	ENST00000430379.5 linkuse as main transcript	c.206C>T	p.Ala69Val	missense_variant	3/7	3		ENSP00000388986.1	C9JPE1
SLC25A20	ENST00000440964.1 linkuse as main transcript	n.*255C>T		non_coding_transcript_exon_variant	6/10	2		ENSP00000388563.1	F8WEF6
SLC25A20	ENST00000440964.1 linkuse as main transcript	n.*255C>T		3_prime_UTR_variant	6/10	2		ENSP00000388563.1	F8WEF6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000687

AC:

AN:

1456580

Hom.:

Cov.:

AF XY:

0.00000966

AC XY:

AN XY:

725002

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000903

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Feb 06, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

.;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

T;D

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.1

.;L

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.7

N;D

REVEL

Uncertain

0.51

Sift

Benign

0.29

T;D

Sift4G

Benign

0.26

T;T

Polyphen

0.24

B;P

Vest4

0.76

MutPred

0.42

.;Loss of disorder (P = 0.0785);

MVP

0.86

MPC

0.34

ClinPred

0.89

GERP RS

5.6

Varity_R

0.67

gMVP

0.56

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over