Genetic Variant SLC25A20:c.*577dupT (chr3-48857132-T-TA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_000387.6(SLC25A20):c.*577dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 146,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 31)

Exomes 𝑓: 0.082 ( 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

Publications

0 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 links:

PRKAR2A-AS1 (HGNC:40471): (PRKAR2A antisense RNA 1)

PRKAR2A-AS1 links:

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ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A20	NM_000387.6 link	c.*577dupT		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	ENST00000319017.5 link	c.*577dupT	3_prime_UTR_variant	Exon 9 of 9	1	NM_000387.6	ENSP00000326305.4	O43772
SLC25A20	ENST00000430379.5 link	c.*577dupT	3_prime_UTR_variant	Exon 7 of 7	3		ENSP00000388986.1	C9JPE1
PRKAR2A-AS1	ENST00000721545.1 link	n.396+8736dupA	intron_variant	Intron 2 of 2
SLC25A20	ENST00000479050.1 link	n.*108dupT	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000641

AC:

AN:

143480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000815

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000281

Gnomad ASJ

AF:

0.000295

Gnomad EAS

AF:

0.000604

Gnomad SAS

AF:

0.00110

Gnomad FIN

AF:

0.00137

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000506

Gnomad OTH

AF:

0.00103

GnomAD4 exome

AF:

0.0817

AC:

207

AN:

2534

Hom.:

Cov.:

AF XY:

0.0837

AC XY:

111

AN XY:

1326

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0672

AC:

AN:

640

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.0750

AC:

AN:

South Asian (SAS)

AF:

0.0684

AC:

AN:

234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0907

AC:

135

AN:

1488

Other (OTH)

AF:

0.0833

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.284

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000641

AC:

AN:

143522

Hom.:

Cov.:

AF XY:

0.000748

AC XY:

AN XY:

69550

show subpopulations

African (AFR)

AF:

0.000813

AC:

AN:

39342

American (AMR)

AF:

0.000280

AC:

AN:

14264

Ashkenazi Jewish (ASJ)

AF:

0.000295

AC:

AN:

3386

East Asian (EAS)

AF:

0.000606

AC:

AN:

4954

South Asian (SAS)

AF:

0.000885

AC:

AN:

4522

European-Finnish (FIN)

AF:

0.00137

AC:

AN:

8752

Middle Eastern (MID)

AF:

0.00355

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000506

AC:

AN:

65174

Other (OTH)

AF:

0.00102

AC:

AN:

1954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

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

PhyloP100

0.54

Mutation Taster

=100/0

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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3-48857132-T-TA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over