rs4646305

chr5-132382847-G-Achr5-132382847-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003060.4(SLC22A5):c.498-1300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 152,132 control chromosomes in the GnomAD database, including 611 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.080 (611 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A5	NM_003060.4	c.498-1300G>A		intron_variant		ENST00000245407.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A5	ENST00000245407.8	c.498-1300G>A		intron_variant		1	NM_003060.4	P1

Frequencies

GnomAD3 genomes AF: 0.0802 AC: 12193 AN: 152014 Hom.: 614 Cov.: 32

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.0791

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0802 AC: 12197 AN: 152132 Hom.: 611 Cov.: 32 AF XY: 0.0797 AC XY: 5927 AN XY: 74364

Gnomad4 AFR AF: 0.0727

Gnomad4 AMR AF: 0.0510

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.0722

Gnomad4 FIN AF: 0.0772

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.0792

Alfa AF: 0.0763 Hom.: 468

Bravo AF: 0.0782

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.8
Dann	Benign	0.27

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: rs4646305; hg19: chr5-131718539;