5-132371601-A-G

Variant names:

• chr5-132371601-A-G
• rs2631362
• NM_003060.4:c.393+1236A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003060.4(SLC22A5):​c.393+1236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,966 control chromosomes in the GnomAD database, including 6,947 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 0.29 (6947 hom., cov: 31)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 20 publications found

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 Gene-Disease associations (from GenCC):

• systemic primary carnitine deficiency disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• short QT syndrome

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003060.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	NM_003060.4	MANE Select	c.393+1236A>G		intron	N/A	NP_003051.1
	SLC22A5	NM_001308122.2		c.393+1236A>G		intron	N/A	NP_001295051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	ENST00000245407.8	TSL:1 MANE Select	c.393+1236A>G		intron	N/A	ENSP00000245407.3
	SLC22A5	ENST00000435065.7	TSL:1	c.393+1236A>G		intron	N/A	ENSP00000402760.2
	SLC22A5	ENST00000448810.6	TSL:1	n.393+1236A>G		intron	N/A	ENSP00000401860.2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43484 AN: 151848 Hom.: 6946 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.286 AC: 43495 AN: 151966 Hom.: 6947 Cov.: 31 AF XY: 0.298 AC XY: 22157 AN XY: 74256

African (AFR) AF: 0.167 AC: 6939 AN: 41464

American (AMR) AF: 0.289 AC: 4415 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3462

East Asian (EAS) AF: 0.375 AC: 1930 AN: 5150

South Asian (SAS) AF: 0.560 AC: 2689 AN: 4800

European-Finnish (FIN) AF: 0.428 AC: 4506 AN: 10538

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21134 AN: 67958

Other (OTH) AF: 0.288 AC: 607 AN: 2106

Alfa AF: 0.299 Hom.: 11932

Bravo AF: 0.263

Asia WGS AF: 0.463 AC: 1609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.5
DANN	Benign	0.66
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2631362; hg19: chr5-131707293;