rs2073643

Variant names:

• chr5-132387596-T-C
• rs2073643
• NM_003060.4:c.951+445T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-132387596-T-C
• chr5-132387596-T-G

Variant summary

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

The NM_003060.4(SLC22A5):​c.951+445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,494 control chromosomes in the GnomAD database, including 16,730 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 0.46 (16730 hom., cov: 31)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 63 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	NM_003060.4	MANE Select	c.951+445T>C		intron	N/A	NP_003051.1
	SLC22A5	NM_001308122.2		c.1023+445T>C		intron	N/A	NP_001295051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	ENST00000245407.8	TSL:1 MANE Select	c.951+445T>C		intron	N/A	ENSP00000245407.3
	SLC22A5	ENST00000435065.7	TSL:1	c.1023+445T>C		intron	N/A	ENSP00000402760.2
	SLC22A5	ENST00000448810.6	TSL:1	n.951+445T>C		intron	N/A	ENSP00000401860.2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69821 AN: 151376 Hom.: 16716 Cov.: 31

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.461 AC: 69862 AN: 151494 Hom.: 16730 Cov.: 31 AF XY: 0.447 AC XY: 33057 AN XY: 74030

African (AFR) AF: 0.397 AC: 16409 AN: 41296

American (AMR) AF: 0.410 AC: 6256 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1953 AN: 3466

East Asian (EAS) AF: 0.301 AC: 1551 AN: 5160

South Asian (SAS) AF: 0.198 AC: 952 AN: 4820

European-Finnish (FIN) AF: 0.412 AC: 4319 AN: 10472

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36558 AN: 67738

Other (OTH) AF: 0.490 AC: 1030 AN: 2102

Alfa AF: 0.518 Hom.: 95256

Bravo AF: 0.465

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.8
DANN	Benign	0.75
PhyloP100		0.31
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: rs2073643; hg19: chr5-131723288;