Genetic Variant SLC25A20:c.*577delT (chr3-48857132-TA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000387.6(SLC25A20):c.*577delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 145,974 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 31)

Exomes 𝑓: 0.065 ( 0 hom. )

Consequence

SLC25A20
NM_000387.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.539

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A20	NM_000387.6 link	c.*577delT		3_prime_UTR_variant	Exon 9 of 9	ENST00000319017.5	NP_000378.1	O43772

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC25A20	ENST00000319017 link	c.*577delT	3_prime_UTR_variant	Exon 9 of 9	1	NM_000387.6	ENSP00000326305.4	O43772
SLC25A20	ENST00000430379 link	c.*577delT	3_prime_UTR_variant	Exon 7 of 7	3		ENSP00000388986.1	C9JPE1
SLC25A20	ENST00000479050.1 link	n.*108delT	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

191

AN:

143432

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00119

Gnomad ASJ

AF:

0.000591

Gnomad EAS

AF:

0.000604

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.00263

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000767

Gnomad OTH

AF:

0.00155

GnomAD4 exome

AF:

0.0651

AC:

163

AN:

2502

Hom.:

Cov.:

AF XY:

0.0620

AC XY:

AN XY:

1306

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

Gnomad4 AMR exome

AF:

0.0540

AC:

AN:

630

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

Gnomad4 EAS exome

AF:

0.0526

AC:

AN:

Gnomad4 SAS exome

AF:

0.0517

AC:

AN:

232

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

Gnomad4 NFE exome

AF:

0.0740

AC:

109

AN:

1472

Gnomad4 Remaining exome

AF:

0.0638

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00133

AC:

191

AN:

143472

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

100

AN XY:

69516

show subpopulations

Gnomad4 AFR

AF:

0.00196

AC:

0.0019573

AN:

0.0019573

Gnomad4 AMR

AF:

0.00119

AC:

0.00119399

AN:

0.00119399

Gnomad4 ASJ

AF:

0.000591

AC:

0.000590667

AN:

0.000590667

Gnomad4 EAS

AF:

0.000606

AC:

0.000606061

AN:

0.000606061

Gnomad4 SAS

AF:

0.00354

AC:

0.00353826

AN:

0.00353826

Gnomad4 FIN

AF:

0.00263

AC:

0.00263098

AN:

0.00263098

Gnomad4 NFE

AF:

0.000767

AC:

0.000767177

AN:

0.000767177

Gnomad4 OTH

AF:

0.00154

AC:

0.00154162

AN:

0.00154162

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000325

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Carnitine acylcarnitine translocase deficiency

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

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

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