NM_003060.4:c.-234C>G

Variant names:

• chr5-132369739-C-G
• rs4646300
• NM_003060.4:c.-234C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003060.4(SLC22A5):​c.-234C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 477,616 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (15 hom.)
• Consequence: SLC22A5 NM_003060.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.160
• Publications: 1 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-132369739-C-G is Benign according to our data. Variant chr5-132369739-C-G is described in ClinVar as [Benign]. Clinvar id is 904881.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.-234C>G		5_prime_UTR_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.-234C>G		5_prime_UTR_variant	Exon 1 of 10	1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 314 AN: 152098 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0580

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00198 AC: 645 AN: 325410 Hom.: 15 Cov.: 4 AF XY: 0.00189 AC XY: 316 AN XY: 167286

African (AFR) AF: 0.00 AC: 0 AN: 7368

American (AMR) AF: 0.000137 AC: 1 AN: 7326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10110

East Asian (EAS) AF: 0.0251 AC: 569 AN: 22694

South Asian (SAS) AF: 0.0000624 AC: 1 AN: 16028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1520

European-Non Finnish (NFE) AF: 0.0000417 AC: 9 AN: 215818

Other (OTH) AF: 0.00329 AC: 65 AN: 19766

GnomAD4 genome AF: 0.00207 AC: 315 AN: 152206 Hom.: 6 Cov.: 33 AF XY: 0.00226 AC XY: 168 AN XY: 74430

African (AFR) AF: 0.0000241 AC: 1 AN: 41554

American (AMR) AF: 0.000327 AC: 5 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0582 AC: 301 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67988

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.000624 Hom.: 0

Bravo AF: 0.00243

Asia WGS AF: 0.0120 AC: 40 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Renal carnitine transport defect Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.9
DANN	Benign	0.50
PhyloP100		0.16
PromoterAI		-0.20	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs4646300; hg19: chr5-131705431;