NM_003060.4:c.824+558C>G

Variant names:

• chr5-132386057-C-G
• rs7731390
• NM_003060.4:c.824+558C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003060.4(SLC22A5):​c.824+558C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 152,278 control chromosomes in the GnomAD database, including 90 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 0.027 (90 hom., cov: 33)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0269 (4099/152278) while in subpopulation NFE AF= 0.0426 (2898/68012). AF 95% confidence interval is 0.0413. There are 90 homozygotes in gnomad4. There are 2017 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 90 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.824+558C>G		intron_variant	Intron 4 of 9	ENST00000245407.8	NP_003051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8	c.824+558C>G		intron_variant	Intron 4 of 9	1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4098 AN: 152160 Hom.: 90 Cov.: 33

Gnomad AFR AF: 0.00719

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0269 AC: 4099 AN: 152278 Hom.: 90 Cov.: 33 AF XY: 0.0271 AC XY: 2017 AN XY: 74466

Gnomad4 AFR AF: 0.00717

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.0450

Gnomad4 NFE AF: 0.0426

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0353 Hom.: 20

Bravo AF: 0.0224

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.3
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs7731390; hg19: chr5-131721749;