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. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_000387.6(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 NM_000387.6 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

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 Benign. Variant got -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 id is 529871.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chr3-48862536-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome 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 gnomad4_exome. There are 174 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A20	NM_000387.6	c.535+6C>T		splice_region_variant, intron_variant	Intron 5 of 8	ENST00000319017.5	NP_000378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A20	ENST00000319017.5	c.535+6C>T		splice_region_variant, intron_variant	Intron 5 of 8	1	NM_000387.6	ENSP00000326305.4
SLC25A20	ENST00000430379.5	c.316+6C>T		splice_region_variant, intron_variant	Intron 3 of 6	3		ENSP00000388986.1
SLC25A20	ENST00000440964.1	n.*365+6C>T		splice_region_variant, intron_variant	Intron 6 of 9	2		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

GnomAD3 exomes AF: 0.000374 AC: 94 AN: 251416 Hom.: 2 AF XY: 0.000353 AC XY: 48 AN XY: 135896

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 SAS exome AF: 0.000196

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

Gnomad4 AFR exome AF: 0.000181

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00565

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000140

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000802

Gnomad4 OTH exome AF: 0.000819

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

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000752 Hom.: 0

Bravo AF: 0.000298

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Carnitine acylcarnitine translocase deficiency Uncertain:1 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Feb 23, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs199770033; hg19: chr3-48899969;