Genetic Variant NM_000387.6:c.*577delT (chr3-48857132-TA-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS1_Supporting

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

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: Likely_benign. The variant received -1 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00133 (191/143472) while in subpopulation SAS AF = 0.00354 (16/4522). AF 95% confidence interval is 0.00222. There are 1 homozygotes in GnomAd4. There are 100 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.*577delT		3_prime_UTR	Exon 9 of 9	NP_000378.1	O43772

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC25A20	ENST00000319017.5	TSL:1 MANE Select	c.*577delT	3_prime_UTR	Exon 9 of 9	ENSP00000326305.4	O43772
SLC25A20	ENST00000880877.1		c.*577delT	3_prime_UTR	Exon 9 of 9	ENSP00000550936.1
SLC25A20	ENST00000880878.1		c.*577delT	3_prime_UTR	Exon 7 of 7	ENSP00000550937.1

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

⚠️ 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:

0.0540

AC:

AN:

630

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0526

AC:

AN:

South Asian (SAS)

AF:

0.0517

AC:

AN:

232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0740

AC:

109

AN:

1472

Other (OTH)

AF:

0.0638

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.269

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

African (AFR)

AF:

0.00196

AC:

AN:

39340

American (AMR)

AF:

0.00119

AC:

AN:

14238

Ashkenazi Jewish (ASJ)

AF:

0.000591

AC:

AN:

3386

East Asian (EAS)

AF:

0.000606

AC:

AN:

4950

South Asian (SAS)

AF:

0.00354

AC:

AN:

4522

European-Finnish (FIN)

AF:

0.00263

AC:

AN:

8742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000767

AC:

AN:

65174

Other (OTH)

AF:

0.00154

AC:

AN:

1946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Carnitine acylcarnitine translocase deficiency (1)

Computational scores

Source: dbNSFP v4.9

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over