rs545212823

Variant names:

• chr3-48857234-C-A
• rs545212823
• NM_000387.6:c.*476G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_000387.6(SLC25A20):​c.*476G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 189,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00096 (0 hom.)
• Consequence: SLC25A20 NM_000387.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.198
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00137 (209/152308) while in subpopulation NFE AF = 0.00226 (154/68034). AF 95% confidence interval is 0.00197. There are 0 homozygotes in GnomAd4. There are 87 alleles in the male GnomAd4 subpopulation. Median coverage is 32. 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.*476G>T		3_prime_UTR	Exon 9 of 9	NP_000378.1	O43772

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A20	ENST00000319017.5	TSL:1 MANE Select	c.*476G>T		3_prime_UTR	Exon 9 of 9	ENSP00000326305.4	O43772
	SLC25A20	ENST00000880877.1		c.*476G>T		3_prime_UTR	Exon 9 of 9	ENSP00000550936.1
	SLC25A20	ENST00000880878.1		c.*476G>T		3_prime_UTR	Exon 7 of 7	ENSP00000550937.1

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 208 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00225

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000963 AC: 36 AN: 37394 Hom.: 0 Cov.: 0 AF XY: 0.000916 AC XY: 18 AN XY: 19644

African (AFR) AF: 0.00 AC: 0 AN: 1162

American (AMR) AF: 0.000587 AC: 2 AN: 3408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 788

East Asian (EAS) AF: 0.00 AC: 0 AN: 2346

South Asian (SAS) AF: 0.000215 AC: 1 AN: 4656

European-Finnish (FIN) AF: 0.000879 AC: 1 AN: 1138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.00145 AC: 32 AN: 22032

Other (OTH) AF: 0.00 AC: 0 AN: 1776

GnomAD4 genome AF: 0.00137 AC: 209 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74470

African (AFR) AF: 0.000313 AC: 13 AN: 41566

American (AMR) AF: 0.000589 AC: 9 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00264 AC: 28 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00226 AC: 154 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.00121

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Carnitine acylcarnitine translocase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.66
PhyloP100		0.20

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: rs545212823; hg19: chr3-48894667;