NM_003060.4:c.59T>C

Variant names:

• chr5-132370031-T-C
• NM_003060.4:c.59T>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003060.4(SLC22A5):​c.59T>C​(p.Leu20Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC22A5 NM_003060.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30

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]

MIR3936HG (HGNC:40538): (MIR3936 host gene)

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.956

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.59T>C	p.Leu20Pro	missense_variant	Exon 1 of 10	ENST00000245407.8	NP_003051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8	c.59T>C	p.Leu20Pro	missense_variant	Exon 1 of 10	1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461122 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726924

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T;.
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.83	T;D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Pathogenic	3.6	H;H
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Pathogenic	0.70
Sift	Benign	0.11	T;T
Sift4G	Benign	0.095	T;T
Polyphen		0.90	P;.
Vest4		0.79
MutPred		0.82		Loss of stability (P = 0.0129);Loss of stability (P = 0.0129);
MVP		0.98
MPC		0.73
ClinPred		0.94	D
GERP RS		5.2
Varity_R		0.82
gMVP		0.96

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: chr5-131705723;