5-132390140-G-C

Variant names:

• chr5-132390140-G-C
• rs274553
• NM_003060.4:c.1053-550G>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.1053-550G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 187,624 control chromosomes in the GnomAD database, including 58,070 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 0.76 (45834 hom., cov: 33)
  • Exomes 𝑓: 0.83 (12236 hom.)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.567
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.1053-550G>C		intron_variant	Intron 6 of 9	ENST00000245407.8	NP_003051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8	c.1053-550G>C		intron_variant	Intron 6 of 9	1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116243 AN: 152038 Hom.: 45828 Cov.: 33

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.797

GnomAD4 exome AF: 0.827 AC: 29318 AN: 35468 Hom.: 12236 Cov.: 0 AF XY: 0.826 AC XY: 15570 AN XY: 18850

African (AFR) AF: 0.507 AC: 311 AN: 614

American (AMR) AF: 0.808 AC: 2774 AN: 3432

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 490 AN: 562

East Asian (EAS) AF: 0.908 AC: 1915 AN: 2110

South Asian (SAS) AF: 0.817 AC: 4059 AN: 4966

European-Finnish (FIN) AF: 0.852 AC: 874 AN: 1026

Middle Eastern (MID) AF: 0.767 AC: 69 AN: 90

European-Non Finnish (NFE) AF: 0.831 AC: 17501 AN: 21052

Other (OTH) AF: 0.820 AC: 1325 AN: 1616

GnomAD4 genome AF: 0.764 AC: 116289 AN: 152156 Hom.: 45834 Cov.: 33 AF XY: 0.768 AC XY: 57115 AN XY: 74392

African (AFR) AF: 0.551 AC: 22841 AN: 41476

American (AMR) AF: 0.814 AC: 12456 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3032 AN: 3472

East Asian (EAS) AF: 0.910 AC: 4721 AN: 5186

South Asian (SAS) AF: 0.833 AC: 4014 AN: 4818

European-Finnish (FIN) AF: 0.869 AC: 9209 AN: 10596

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57354 AN: 67994

Other (OTH) AF: 0.790 AC: 1669 AN: 2112

Alfa AF: 0.793 Hom.: 5758

Bravo AF: 0.753

Asia WGS AF: 0.809 AC: 2811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.41
PhyloP100		0.57
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: rs274553; hg19: chr5-131725832;