NM_003060.4:c.-231G>C

Variant names:

• chr5-132369742-G-C
• rs1751803560
• NM_003060.4:c.-231G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003060.4(SLC22A5):​c.-231G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC22A5 NM_003060.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.247
• Publications: 0 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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.-231G>C		5_prime_UTR	Exon 1 of 10	NP_003051.1	O76082-1
	SLC22A5	NM_001308122.2		c.-231G>C		5_prime_UTR	Exon 1 of 11	NP_001295051.1	O76082-3
	MIR3936HG	NR_110997.1		n.73+102C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	ENST00000245407.8	TSL:1 MANE Select	c.-231G>C		5_prime_UTR	Exon 1 of 10	ENSP00000245407.3	O76082-1
	MIR3936HG	ENST00000621103.4	TSL:1	n.73+102C>G		intron	N/A
	SLC22A5	ENST00000893299.1		c.-231G>C		5_prime_UTR	Exon 1 of 10	ENSP00000563358.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 331478 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 170308

African (AFR) AF: 0.00 AC: 0 AN: 7464

American (AMR) AF: 0.00 AC: 0 AN: 7420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10230

East Asian (EAS) AF: 0.00 AC: 0 AN: 22830

South Asian (SAS) AF: 0.00 AC: 0 AN: 16726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1548

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 220182

Other (OTH) AF: 0.00 AC: 0 AN: 20086

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Renal carnitine transport defect (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.65
PhyloP100		0.25
PromoterAI		0.21	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1751803560; hg19: chr5-131705434;