rs274571

Variant names:

• chr5-132376433-A-G
• rs274571
• NM_003060.4:c.394-1945A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-132376433-A-G
• chr5-132376433-A-T

Variant summary

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

The NM_003060.4(SLC22A5):​c.394-1945A>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 152,000 control chromosomes in the GnomAD database, including 6,937 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 (6934 hom., cov: 31)
  • Exomes 𝑓: 0.21 (3 hom.)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.394-1945A>G		intron_variant	Intron 1 of 9	ENST00000245407.8	NP_003051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8	c.394-1945A>G		intron_variant	Intron 1 of 9	1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43435 AN: 151776 Hom.: 6933 Cov.: 31

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.208 AC: 22 AN: 106 Hom.: 3 Cov.: 0 AF XY: 0.218 AC XY: 17 AN XY: 78

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.195 AC: 16 AN: 82

Other (OTH) AF: 0.300 AC: 3 AN: 10

GnomAD4 genome AF: 0.286 AC: 43446 AN: 151894 Hom.: 6934 Cov.: 31 AF XY: 0.298 AC XY: 22122 AN XY: 74218

African (AFR) AF: 0.167 AC: 6929 AN: 41454

American (AMR) AF: 0.289 AC: 4405 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3468

East Asian (EAS) AF: 0.376 AC: 1941 AN: 5158

South Asian (SAS) AF: 0.560 AC: 2678 AN: 4784

European-Finnish (FIN) AF: 0.426 AC: 4499 AN: 10550

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

European-Non Finnish (NFE) AF: 0.311 AC: 21118 AN: 67920

Other (OTH) AF: 0.287 AC: 603 AN: 2104

Alfa AF: 0.298 Hom.: 11959

Bravo AF: 0.263

Asia WGS AF: 0.463 AC: 1608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0020
DANN	Benign	0.71
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs274571; hg19: chr5-131712125; COSMIC: COSV55373681;