5-132385512-T-C

Variant names:

• chr5-132385512-T-C
• rs274557
• NM_003060.4:c.824+13T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003060.4(SLC22A5):​c.824+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,609,746 control chromosomes in the GnomAD database, including 137,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13078 hom., cov: 33)
  • Exomes 𝑓: 0.40 (124506 hom.)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.144

Genes affected

SLC22A5 (HGNC:10969): (solute carrier family 22 member 5) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is a plasma integral membrane protein which functions both as an organic cation transporter and as a sodium-dependent high affinity carnitine transporter. The encoded protein is involved in the active cellular uptake of carnitine. Mutations in this gene are the cause of systemic primary carnitine deficiency (CDSP), an autosomal recessive disorder manifested early in life by hypoketotic hypoglycemia and acute metabolic decompensation, and later in life by skeletal myopathy or cardiomyopathy. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-132385512-T-C is Benign according to our data. Variant chr5-132385512-T-C is described in ClinVar as [Benign]. Clinvar id is 94102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-132385512-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.824+13T>C		intron_variant	Intron 4 of 9	ENST00000245407.8	NP_003051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8	c.824+13T>C		intron_variant	Intron 4 of 9	1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61669 AN: 151988 Hom.: 13070 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.391

GnomAD3 exomes AF: 0.435 AC: 109129 AN: 250752 Hom.: 25281 AF XY: 0.448 AC XY: 60669 AN XY: 135536

Gnomad AFR exome AF: 0.357

Gnomad AMR exome AF: 0.315

Gnomad ASJ exome AF: 0.402

Gnomad EAS exome AF: 0.643

Gnomad SAS exome AF: 0.627

Gnomad FIN exome AF: 0.508

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.421

GnomAD4 exome AF: 0.404 AC: 589082 AN: 1457640 Hom.: 124506 Cov.: 33 AF XY: 0.412 AC XY: 298653 AN XY: 725370

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.621

Gnomad4 FIN exome AF: 0.505

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.406 AC: 61709 AN: 152106 Hom.: 13078 Cov.: 33 AF XY: 0.417 AC XY: 30994 AN XY: 74350

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.391

Alfa AF: 0.392 Hom.: 16554

Bravo AF: 0.385

Asia WGS AF: 0.617 AC: 2145 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Renal carnitine transport defect Benign:5

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 20, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:3

Dec 07, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Apr 18, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary:The c.824+13T>C in SLC22A5 gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 44%, including numerous homozygous occurrences. The observed frequency exceeds the maximum expected allele frequency for a pathogenic SLC22A variant, suggesting that it is a common polymorphism. In addition, the variant has been reported as Benign/Polymorphism by reputable database/clinical laboratory and published reports (Tang et al., 2002). Taken together, this variant has been classified as Benign. -

Mar 03, 2015

GeneDx

Significance: 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	-0.82
CADD	Benign	2.0
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs274557; hg19: chr5-131721204; COSMIC: COSV55372528; COSMIC: COSV55372528;