5-132369834-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003060.4(SLC22A5):c.-139G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 1,126,112 control chromosomes in the GnomAD database, including 5,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.077 (574 hom., cov: 33)
  • Exomes 𝑓: 0.085 (4576 hom.)
• Consequence: SLC22A5 NM_003060.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.927

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-132369834-G-T is Benign according to our data. Variant chr5-132369834-G-T is described in ClinVar as [Benign]. Clinvar id is 350807.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A5	NM_003060.4	c.-139G>T		5_prime_UTR_variant	1/10	ENST00000245407.8
MIR3936HG	NR_110997.1	n.73+10C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A5	ENST00000245407.8	c.-139G>T		5_prime_UTR_variant	1/10	1	NM_003060.4	P1
MIR3936HG	ENST00000621103.4	n.73+10C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11673 AN: 152076 Hom.: 577 Cov.: 33

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0752

GnomAD4 exome AF: 0.0851 AC: 82928 AN: 973926 Hom.: 4576 Cov.: 13 AF XY: 0.0841 AC XY: 40752 AN XY: 484542

Gnomad4 AFR exome AF: 0.0674

Gnomad4 AMR exome AF: 0.0465

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.0560

Gnomad4 FIN exome AF: 0.0751

Gnomad4 NFE exome AF: 0.0789

Gnomad4 OTH exome AF: 0.0863

GnomAD4 genome AF: 0.0767 AC: 11671 AN: 152186 Hom.: 574 Cov.: 33 AF XY: 0.0758 AC XY: 5641 AN XY: 74400

Gnomad4 AFR AF: 0.0617

Gnomad4 AMR AF: 0.0494

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.0648

Gnomad4 FIN AF: 0.0754

Gnomad4 NFE AF: 0.0766

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.0753 Hom.: 71

Bravo AF: 0.0746

Asia WGS AF: 0.124 AC: 429 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Renal carnitine transport defect Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.5
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs13180169; hg19: chr5-131705526;