3-48857132-TA-T

Variant names:

• chr3-48857132-TA-T
• rs533476473
• NM_000387.6:c.*577delT

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.539
• Publications: 0 publications found

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]

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

ACMG classification

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

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00133 AC: 191 AN: 143432 Hom.: 1 Cov.: 31

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.: 0 Cov.: 0 AF XY: 0.0620 AC XY: 81 AN XY: 1306

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

African (AFR) AF: 0.00 AC: 0 AN: 14

American (AMR) AF: 0.0540 AC: 34 AN: 630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12

East Asian (EAS) AF: 0.0526 AC: 2 AN: 38

South Asian (SAS) AF: 0.0517 AC: 12 AN: 232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0740 AC: 109 AN: 1472

Other (OTH) AF: 0.0638 AC: 6 AN: 94

⚠️ 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.

GnomAD4 genome AF: 0.00133 AC: 191 AN: 143472 Hom.: 1 Cov.: 31 AF XY: 0.00144 AC XY: 100 AN XY: 69516

African (AFR) AF: 0.00196 AC: 77 AN: 39340

American (AMR) AF: 0.00119 AC: 17 AN: 14238

Ashkenazi Jewish (ASJ) AF: 0.000591 AC: 2 AN: 3386

East Asian (EAS) AF: 0.000606 AC: 3 AN: 4950

South Asian (SAS) AF: 0.00354 AC: 16 AN: 4522

European-Finnish (FIN) AF: 0.00263 AC: 23 AN: 8742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000767 AC: 50 AN: 65174

Other (OTH) AF: 0.00154 AC: 3 AN: 1946

Alfa AF: 0.000325 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54
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

Other links and lift over

dbSNP: rs533476473; hg19: chr3-48894565; COSMIC: COSV59803064; COSMIC: COSV59803064;