rs4646301

chr5-132375408-G-A

Variant summary

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

The NM_003060.4(SLC22A5):c.394-2970G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 152,270 control chromosomes in the GnomAD database, including 579 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 0.077 (579 hom., cov: 32)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.85).
• 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.394-2970G>A		intron_variant		ENST00000245407.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A5	ENST00000245407.8	c.394-2970G>A		intron_variant		1	NM_003060.4	P1

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11688 AN: 152152 Hom.: 582 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.0769

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0754

Gnomad OTH AF: 0.0770

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0768 AC: 11691 AN: 152270 Hom.: 579 Cov.: 32 AF XY: 0.0763 AC XY: 5684 AN XY: 74456

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.0497

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.0729

Gnomad4 FIN AF: 0.0769

Gnomad4 NFE AF: 0.0754

Gnomad4 OTH AF: 0.0771

Alfa AF: 0.0754 Hom.: 571

Bravo AF: 0.0741

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.2
Dann	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4646301; hg19: chr5-131711100;