rs1553686314

Positions:

• chr3-48883995-ACCTGAGCACATCTTCTGGGTGTTTCTGTTGTAGTTTCTTCCCCAAACCAAACCCAAAGAAGCACACGGCAAACATGGGAGTGACCCCGATGATAGGGGCAGCCATTCCCCGATATAGCCCCGTGATGC-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_000387.6(SLC25A20):​c.200_326+1del​(p.Gly67fs) variant causes a frameshift, splice donor, splice region, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC25A20 NM_000387.6 frameshift, splice_donor, splice_region, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.91

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-48883995-ACCTGAGCACATCTTCTGGGTGTTTCTGTTGTAGTTTCTTCCCCAAACCAAACCCAAAGAAGCACACGGCAAACATGGGAGTGACCCCGATGATAGGGGCAGCCATTCCCCGATATAGCCCCGTGATGC-A is Pathogenic according to our data. Variant chr3-48883995-ACCTGAGCACATCTTCTGGGTGTTTCTGTTGTAGTTTCTTCCCCAAACCAAACCCAAAGAAGCACACGGCAAACATGGGAGTGACCCCGATGATAGGGGCAGCCATTCCCCGATATAGCCCCGTGATGC-A is described in ClinVar as [Pathogenic]. Clinvar id is 12133.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A20	NM_000387.6	c.200_326+1del	p.Gly67fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	3/9	ENST00000319017.5	NP_000378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A20	ENST00000319017.5	c.200_326+1del	p.Gly67fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	3/9	1	NM_000387.6	ENSP00000326305.4
SLC25A20	ENST00000430379.5	c.198+7857_198+7984del		intron_variant		3		ENSP00000388986.1
SLC25A20	ENST00000440964.1	n.*30_*156+1del		splice_region_variant, non_coding_transcript_exon_variant	4/10	2		ENSP00000388563.1
SLC25A20	ENST00000440964.1	n.*30_*156+1del		splice_donor_variant, 3_prime_UTR_variant, intron_variant	4/10	2		ENSP00000388563.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Carnitine acylcarnitine translocase deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 1998

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553686314; hg19: chr3-48921428;