chr5-132378414-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003060.4(SLC22A5):c.430C>T(p.Leu144Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,614,242 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 103 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 128 hom. )

Consequence

SLC22A5
NM_003060.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.325

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027811527).

BP6

Variant 5-132378414-C-T is Benign according to our data. Variant chr5-132378414-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 25373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-132378414-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4 link	c.430C>T	p.Leu144Phe	missense_variant	Exon 2 of 10	ENST00000245407.8	NP_003051.1	O76082-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8 link	c.430C>T	p.Leu144Phe	missense_variant	Exon 2 of 10	1	NM_003060.4	ENSP00000245407.3		O76082-1

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3290

AN:

152250

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0761

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00579

AC:

1456

AN:

251494

Hom.:

AF XY:

0.00413

AC XY:

562

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0788

Gnomad AMR exome

AF:

0.00382

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00222

AC:

3252

AN:

1461874

Hom.:

128

Cov.:

AF XY:

0.00192

AC XY:

1393

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0767

Gnomad4 AMR exome

AF:

0.00405

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.00487

GnomAD4 genome

AF:

0.0216

AC:

3297

AN:

152368

Hom.:

103

Cov.:

AF XY:

0.0206

AC XY:

1538

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0761

Gnomad4 AMR

AF:

0.00568

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00394

Hom.:

Bravo

AF:

0.0246

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0822

AC:

362

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00738

AC:

896

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Renal carnitine transport defect

Benign:7

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

May 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 03, 2022

Giacomini Lab, University of California, San Francisco

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: in vitro;research

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Apr 09, 2014

Counsyl

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: literature only

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:2

May 31, 2018

SIB Swiss Institute of Bioinformatics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. BS3 => Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing (PMID:16931768). -

Jan 21, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.57

D;.;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.016

LIST_S2

Uncertain

0.86

D;D;D

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.084

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.10

B;.;.

Vest4

0.18

MVP

0.84

MPC

0.33

ClinPred

0.0073

GERP RS

3.0

Varity_R

0.10

gMVP

0.72

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