rs4646305

Variant names:

• chr5-132382847-G-A
• rs4646305
• NM_003060.4:c.498-1300G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132382847-G-A
• chr5-132382847-G-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.498-1300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 152,132 control chromosomes in the GnomAD database, including 611 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 0.080 (611 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 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.498-1300G>A		intron	N/A	NP_003051.1	O76082-1
	SLC22A5	NM_001308122.2		c.570-1300G>A		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.498-1300G>A		intron	N/A	ENSP00000245407.3	O76082-1
	SLC22A5	ENST00000435065.7	TSL:1	c.570-1300G>A		intron	N/A	ENSP00000402760.2	O76082-3
	SLC22A5	ENST00000448810.6	TSL:1	n.498-1300G>A		intron	N/A	ENSP00000401860.2	H7C1R8

Frequencies

GnomAD3 genomes AF: 0.0802 AC: 12193 AN: 152014 Hom.: 614 Cov.: 32

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.0791

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0802 AC: 12197 AN: 152132 Hom.: 611 Cov.: 32 AF XY: 0.0797 AC XY: 5927 AN XY: 74364

African (AFR) AF: 0.0727 AC: 3018 AN: 41496

American (AMR) AF: 0.0510 AC: 779 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1424 AN: 5172

South Asian (SAS) AF: 0.0722 AC: 348 AN: 4818

European-Finnish (FIN) AF: 0.0772 AC: 817 AN: 10580

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0755 AC: 5135 AN: 68002

Other (OTH) AF: 0.0792 AC: 167 AN: 2108

Alfa AF: 0.0757 Hom.: 604

Bravo AF: 0.0782

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.27
PhyloP100		0.082
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: rs4646305; hg19: chr5-131718539;