rs2073642

chr5-132378082-C-T

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.394-296C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 1,538,810 control chromosomes in the GnomAD database, including 6,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (612 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5421 hom.)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00400

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=-0.85).
• BP6: Variant 5-132378082-C-T is Benign according to our data. Variant chr5-132378082-C-T is described in ClinVar as [Benign]. Clinvar id is 671627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A5	NM_003060.4	c.394-296C>T		intron_variant		ENST00000245407.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A5	ENST00000245407.8	c.394-296C>T		intron_variant		1	NM_003060.4	P1

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 12186 AN: 152110 Hom.: 615 Cov.: 32

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.0769

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.0794

GnomAD4 exome AF: 0.0786 AC: 108943 AN: 1386582 Hom.: 5421 Cov.: 31 AF XY: 0.0781 AC XY: 53396 AN XY: 683348

Gnomad4 AFR exome AF: 0.0698

Gnomad4 AMR exome AF: 0.0380

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.301

Gnomad4 SAS exome AF: 0.0593

Gnomad4 FIN exome AF: 0.0764

Gnomad4 NFE exome AF: 0.0732

Gnomad4 OTH exome AF: 0.0833

GnomAD4 genome AF: 0.0801 AC: 12190 AN: 152228 Hom.: 612 Cov.: 32 AF XY: 0.0795 AC XY: 5919 AN XY: 74430

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.0510

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.0729

Gnomad4 FIN AF: 0.0769

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0753 Hom.: 601

Bravo AF: 0.0782

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Renal carnitine transport defect Benign:2

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.7
Dann	Benign	0.46

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: rs2073642; hg19: chr5-131713774; COSMIC: COSV55375161;