5-132369895-C-T

Variant names:

• chr5-132369895-C-T
• rs13180043
• ENST00000448810.6:n.-78C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003060.4(SLC22A5):​c.-78C>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 0.0794 in 1,557,066 control chromosomes in the GnomAD database, including 6,153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (576 hom., cov: 33)
  • Exomes 𝑓: 0.080 (5577 hom.)
• Consequence: SLC22A5 NM_003060.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.434
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 5-132369895-C-T is Benign according to our data. Variant chr5-132369895-C-T is described in ClinVar as [Benign]. Clinvar id is 25342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.-78C>T		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.-78C>T		5_prime_UTR_variant	Exon 1 of 10	1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11687 AN: 152144 Hom.: 579 Cov.: 33

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.0756

GnomAD4 exome AF: 0.0797 AC: 111940 AN: 1404812 Hom.: 5577 Cov.: 29 AF XY: 0.0792 AC XY: 55089 AN XY: 695708

African (AFR) AF: 0.0597 AC: 1914 AN: 32044

American (AMR) AF: 0.0378 AC: 1416 AN: 37474

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 2727 AN: 23710

East Asian (EAS) AF: 0.296 AC: 11375 AN: 38426

South Asian (SAS) AF: 0.0544 AC: 4327 AN: 79570

European-Finnish (FIN) AF: 0.0777 AC: 3452 AN: 44402

Middle Eastern (MID) AF: 0.0678 AC: 277 AN: 4084

European-Non Finnish (NFE) AF: 0.0751 AC: 81684 AN: 1087070

Other (OTH) AF: 0.0822 AC: 4768 AN: 58032

GnomAD4 genome AF: 0.0768 AC: 11686 AN: 152254 Hom.: 576 Cov.: 33 AF XY: 0.0758 AC XY: 5645 AN XY: 74430

African (AFR) AF: 0.0618 AC: 2567 AN: 41566

American (AMR) AF: 0.0494 AC: 756 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1386 AN: 5152

South Asian (SAS) AF: 0.0647 AC: 313 AN: 4834

European-Finnish (FIN) AF: 0.0747 AC: 793 AN: 10616

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0767 AC: 5216 AN: 67996

Other (OTH) AF: 0.0758 AC: 160 AN: 2112

Alfa AF: 0.0763 Hom.: 63

Bravo AF: 0.0746

Asia WGS AF: 0.124 AC: 429 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Renal carnitine transport defect Benign:3

Apr 19, 2018

Counsyl

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not specified Benign:1

Dec 18, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: SLC22A5 c.-78C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.08 in 31322 control chromosomes in the gnomAD database, including 117 homozygotes. The observed variant frequency is approximately 17.62 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC22A5 causing Systemic Primary Carnitine Deficiency phenotype (0.0046), strongly suggesting that the variant is benign. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -

not provided Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.9
DANN	Benign	0.84
PhyloP100		0.43
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs13180043; hg19: chr5-131705587;