chr3-48857353-G-A

Variant names:

• chr3-48857353-G-A
• rs78776342
• NM_000387.6:c.*357C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000387.6(SLC25A20):​c.*357C>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 0.000882 in 305,112 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (2 hom.)
• Consequence: SLC25A20 NM_000387.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.390
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-48857353-G-A is Benign according to our data. Variant chr3-48857353-G-A is described in ClinVar as Benign. ClinVar VariationId is 345936.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000795 (121/152278) while in subpopulation EAS AF = 0.0227 (118/5188). AF 95% confidence interval is 0.0194. There are 2 homozygotes in GnomAd4. There are 68 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.*357C>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.*357C>T		3_prime_UTR	Exon 9 of 9	ENSP00000326305.4	O43772
	SLC25A20	ENST00000880877.1		c.*357C>T		3_prime_UTR	Exon 9 of 9	ENSP00000550936.1
	SLC25A20	ENST00000880878.1		c.*357C>T		3_prime_UTR	Exon 7 of 7	ENSP00000550937.1

Frequencies

GnomAD3 genomes AF: 0.000795 AC: 121 AN: 152160 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000968 AC: 148 AN: 152834 Hom.: 2 Cov.: 0 AF XY: 0.000889 AC XY: 73 AN XY: 82146

African (AFR) AF: 0.00 AC: 0 AN: 4702

American (AMR) AF: 0.00 AC: 0 AN: 6794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3836

East Asian (EAS) AF: 0.0205 AC: 146 AN: 7130

South Asian (SAS) AF: 0.0000373 AC: 1 AN: 26832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 87964

Other (OTH) AF: 0.000129 AC: 1 AN: 7756

GnomAD4 genome AF: 0.000795 AC: 121 AN: 152278 Hom.: 2 Cov.: 32 AF XY: 0.000913 AC XY: 68 AN XY: 74458

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0227 AC: 118 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000129 Hom.: 0

Bravo AF: 0.000831

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

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	-0.80
CADD	Benign	4.5
DANN	Benign	0.66
PhyloP100		0.39

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: rs78776342; hg19: chr3-48894786;