5-132391988-T-C

Variant names:

• chr5-132391988-T-C
• rs274551
• NM_003060.4:c.1268-445T>C

Variant summary

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

The NM_003060.4(SLC22A5):​c.1268-445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,174 control chromosomes in the GnomAD database, including 45,049 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 0.75 (45049 hom., cov: 32)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 19 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: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet, G2P, ClinGen
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	NM_003060.4	MANE Select	c.1268-445T>C		intron	N/A	NP_003051.1	O76082-1
	SLC22A5	NM_001308122.2		c.1340-445T>C		intron	N/A	NP_001295051.1	O76082-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	ENST00000245407.8	TSL:1 MANE Select	c.1268-445T>C		intron	N/A	ENSP00000245407.3	O76082-1
	SLC22A5	ENST00000435065.7	TSL:1	c.1340-445T>C		intron	N/A	ENSP00000402760.2	O76082-3
	SLC22A5	ENST00000448810.6	TSL:1	n.*120-445T>C		intron	N/A	ENSP00000401860.2	H7C1R8

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114852 AN: 152056 Hom.: 45051 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.755 AC: 114882 AN: 152174 Hom.: 45049 Cov.: 32 AF XY: 0.759 AC XY: 56452 AN XY: 74388

African (AFR) AF: 0.519 AC: 21510 AN: 41476

American (AMR) AF: 0.811 AC: 12410 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3017 AN: 3472

East Asian (EAS) AF: 0.911 AC: 4708 AN: 5168

South Asian (SAS) AF: 0.832 AC: 4010 AN: 4820

European-Finnish (FIN) AF: 0.870 AC: 9224 AN: 10608

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.843 AC: 57357 AN: 68014

Other (OTH) AF: 0.785 AC: 1657 AN: 2110

Alfa AF: 0.815 Hom.: 209645

Bravo AF: 0.742

Asia WGS AF: 0.805 AC: 2798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.062
DANN	Benign	0.34
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs274551; hg19: chr5-131727680;