rs747050292

Variant names:

• chr5-132385381-T-A
• NM_003060.4:c.706T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132385381-T-A
• chr5-132385381-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_003060.4(SLC22A5):​c.706T>A​(p.Cys236Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC22A5 NM_003060.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42

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 Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a transmembrane_region Helical; Name=5 (size 20) in uniprot entity OCTN2_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_003060.4
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.706T>A	p.Cys236Ser	missense_variant	Exon 4 of 10	ENST00000245407.8	NP_003051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8	c.706T>A	p.Cys236Ser	missense_variant	Exon 4 of 10	1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Renal carnitine transport defect Uncertain:1

Nov 21, 2023

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Benign	0.36	T;.;.
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.0	L;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Uncertain	0.39
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.63	T;T;T
Polyphen		0.59	P;.;.
Vest4		0.47
MutPred		0.54		Loss of stability (P = 0.105);.;.;
MVP		0.86
MPC		0.27
ClinPred		0.71	D
GERP RS		5.9
Varity_R		0.59
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-131721073;