rs2631365

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003060.4(SLC22A5):c.285T>C(p.Leu95Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,582,580 control chromosomes in the GnomAD database, including 135,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13132 hom., cov: 33)

Exomes 𝑓: 0.40 ( 121958 hom. )

Consequence

SLC22A5
NM_003060.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.298

Variant links:

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]

SLC22A5 links:

SLC22A5 (HGNC:):

SLC22A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 5-132370257-T-C is Benign according to our data. Variant chr5-132370257-T-C is described in ClinVar as [Benign]. Clinvar id is 94099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-132370257-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.298 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A5	NM_003060.4 linkuse as main transcript	c.285T>C	p.Leu95Leu	synonymous_variant	1/10	ENST00000245407.8	NP_003051.1	O76082-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8 linkuse as main transcript	c.285T>C	p.Leu95Leu	synonymous_variant	1/10	1	NM_003060.4	ENSP00000245407.3		O76082-1

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61787

AN:

151952

Hom.:

13124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.392

GnomAD3 exomes

AF:

0.433

AC:

82365

AN:

190330

Hom.:

18957

AF XY:

0.445

AC XY:

46326

AN XY:

104036

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.635

Gnomad SAS exome

AF:

0.623

Gnomad FIN exome

AF:

0.506

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.405

AC:

579057

AN:

1430510

Hom.:

121958

Cov.:

AF XY:

0.412

AC XY:

292033

AN XY:

708786

show subpopulations

Gnomad4 AFR exome

AF:

0.353

Gnomad4 AMR exome

AF:

0.324

Gnomad4 ASJ exome

AF:

0.400

Gnomad4 EAS exome

AF:

0.668

Gnomad4 SAS exome

AF:

0.620

Gnomad4 FIN exome

AF:

0.505

Gnomad4 NFE exome

AF:

0.379

Gnomad4 OTH exome

AF:

0.415

GnomAD4 genome

AF:

0.407

AC:

61825

AN:

152070

Hom.:

13132

Cov.:

AF XY:

0.417

AC XY:

31020

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.359

Gnomad4 AMR

AF:

0.352

Gnomad4 ASJ

AF:

0.416

Gnomad4 EAS

AF:

0.668

Gnomad4 SAS

AF:

0.642

Gnomad4 FIN

AF:

0.512

Gnomad4 NFE

AF:

0.397

Gnomad4 OTH

AF:

0.392

Alfa

AF:

0.366

Hom.:

4247

Bravo

AF:

0.386

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Renal carnitine transport defect

Benign:7

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Phosphorus, Inc.	Aug 01, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 07, 2017	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 18, 2016	Variant summary: The variant was observed in the general population by the ExAC project at an allele frequency of ~50% across diverse ethnicities including numerous homozygotes indicating the variant to be a neutral polymorphism. Therefore the variant is classified as Benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.6

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over