rs199770033

Variant names:

• chr3-48862536-G-A
• rs199770033
• NM_000387.6:c.535+6C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-48862536-G-A
• chr3-48862536-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The ENST00000319017.5(SLC25A20):​c.535+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 1,598,344 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00030 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (3 hom.)
• Consequence: SLC25A20 ENST00000319017.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001004
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 0.0950
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 3-48862536-G-A is Benign according to our data. Variant chr3-48862536-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 529871.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000242 (350/1446020) while in subpopulation MID AF = 0.00724 (41/5662). AF 95% confidence interval is 0.00549. There are 3 homozygotes in GnomAdExome4. There are 174 alleles in the male GnomAdExome4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000319017.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A20	NM_000387.6	MANE Select	c.535+6C>T		splice_region intron	N/A	NP_000378.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A20	ENST00000319017.5	TSL:1 MANE Select	c.535+6C>T		splice_region intron	N/A	ENSP00000326305.4
	SLC25A20	ENST00000430379.5	TSL:3	c.316+6C>T		splice_region intron	N/A	ENSP00000388986.1
	SLC25A20	ENST00000440964.1	TSL:2	n.*365+6C>T		splice_region intron	N/A	ENSP00000388563.1

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000374 AC: 94 AN: 251416 AF XY: 0.000353

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00625

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000242 AC: 350 AN: 1446020 Hom.: 3 Cov.: 28 AF XY: 0.000242 AC XY: 174 AN XY: 720470

African (AFR) AF: 0.000181 AC: 6 AN: 33178

American (AMR) AF: 0.000157 AC: 7 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00565 AC: 147 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.000140 AC: 12 AN: 85908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00724 AC: 41 AN: 5662

European-Non Finnish (NFE) AF: 0.0000802 AC: 88 AN: 1097706

Other (OTH) AF: 0.000819 AC: 49 AN: 59836

GnomAD4 genome AF: 0.000295 AC: 45 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74484

African (AFR) AF: 0.0000241 AC: 1 AN: 41574

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68030

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000752 Hom.: 0

Bravo AF: 0.000298

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	Carnitine acylcarnitine translocase deficiency (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.64
PhyloP100		0.095
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.020
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: rs199770033; hg19: chr3-48899969;