5-132385512-T-C

Variant names:

• chr5-132385512-T-C
• rs274557
• NM_003060.4:c.824+13T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003060.4(SLC22A5):​c.824+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,609,746 control chromosomes in the GnomAD database, including 137,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13078 hom., cov: 33)
  • Exomes 𝑓: 0.40 (124506 hom.)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.144
• Publications: 45 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-132385512-T-C is Benign according to our data. Variant chr5-132385512-T-C is described in ClinVar as Benign. ClinVar VariationId is 94102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 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.824+13T>C		intron	N/A	NP_003051.1	O76082-1
	SLC22A5	NM_001308122.2		c.896+13T>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.824+13T>C		intron	N/A	ENSP00000245407.3	O76082-1
	SLC22A5	ENST00000435065.7	TSL:1	c.896+13T>C		intron	N/A	ENSP00000402760.2	O76082-3
	SLC22A5	ENST00000448810.6	TSL:1	n.824+13T>C		intron	N/A	ENSP00000401860.2	H7C1R8

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61669 AN: 151988 Hom.: 13070 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.391

GnomAD2 exomes AF: 0.435 AC: 109129 AN: 250752 AF XY: 0.448

Gnomad AFR exome AF: 0.357

Gnomad AMR exome AF: 0.315

Gnomad ASJ exome AF: 0.402

Gnomad EAS exome AF: 0.643

Gnomad FIN exome AF: 0.508

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.421

GnomAD4 exome AF: 0.404 AC: 589082 AN: 1457640 Hom.: 124506 Cov.: 33 AF XY: 0.412 AC XY: 298653 AN XY: 725370

African (AFR) AF: 0.354 AC: 11818 AN: 33416

American (AMR) AF: 0.325 AC: 14515 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 10456 AN: 26112

East Asian (EAS) AF: 0.668 AC: 26484 AN: 39648

South Asian (SAS) AF: 0.621 AC: 53497 AN: 86164

European-Finnish (FIN) AF: 0.505 AC: 26940 AN: 53348

Middle Eastern (MID) AF: 0.471 AC: 2708 AN: 5752

European-Non Finnish (NFE) AF: 0.377 AC: 417593 AN: 1108234

Other (OTH) AF: 0.416 AC: 25071 AN: 60294

GnomAD4 genome AF: 0.406 AC: 61709 AN: 152106 Hom.: 13078 Cov.: 33 AF XY: 0.417 AC XY: 30994 AN XY: 74350

African (AFR) AF: 0.359 AC: 14901 AN: 41498

American (AMR) AF: 0.352 AC: 5373 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1443 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3462 AN: 5168

South Asian (SAS) AF: 0.641 AC: 3095 AN: 4826

European-Finnish (FIN) AF: 0.511 AC: 5398 AN: 10566

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26853 AN: 67980

Other (OTH) AF: 0.391 AC: 828 AN: 2116

Alfa AF: 0.389 Hom.: 20278

Bravo AF: 0.385

Asia WGS AF: 0.617 AC: 2145 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Renal carnitine transport defect (5)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs274557; hg19: chr5-131721204; COSMIC: COSV55372528; COSMIC: COSV55372528;