5-132389258-T-C

Position:

• chr5-132389258-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003060.4(SLC22A5):​c.1052+237T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 493,902 control chromosomes in the GnomAD database, including 165,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (44808 hom., cov: 32)
  • Exomes 𝑓: 0.84 (121017 hom.)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-132389258-T-C is Benign according to our data. Variant chr5-132389258-T-C is described in ClinVar as [Benign]. Clinvar id is 670106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.1052+237T>C		intron_variant		ENST00000245407.8	NP_003051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8	c.1052+237T>C		intron_variant		1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114381 AN: 152004 Hom.: 44808 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.789

GnomAD4 exome AF: 0.839 AC: 286681 AN: 341780 Hom.: 121017 Cov.: 2 AF XY: 0.840 AC XY: 154435 AN XY: 183954

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.815

Gnomad4 ASJ exome AF: 0.879

Gnomad4 EAS exome AF: 0.931

Gnomad4 SAS exome AF: 0.825

Gnomad4 FIN exome AF: 0.871

Gnomad4 NFE exome AF: 0.847

Gnomad4 OTH exome AF: 0.828

GnomAD4 genome AF: 0.752 AC: 114411 AN: 152122 Hom.: 44808 Cov.: 32 AF XY: 0.756 AC XY: 56240 AN XY: 74386

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.783

Alfa AF: 0.822 Hom.: 66556

Bravo AF: 0.739

Asia WGS AF: 0.805 AC: 2796 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.92
CADD	Benign	0.18
DANN	Benign	0.39

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: rs274554; hg19: chr5-131724950;