5-132369766-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003060.4(SLC22A5):c.-207C>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 0.596 in 592,348 control chromosomes in the GnomAD database, including 110,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27799 hom., cov: 33)
  • Exomes 𝑓: 0.60 (82696 hom.)
• Consequence: SLC22A5 NM_003060.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.35

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-132369766-C-G is Benign according to our data. Variant chr5-132369766-C-G is described in ClinVar as [Benign]. Clinvar id is 350806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A5	NM_003060.4	c.-207C>G		5_prime_UTR_variant	1/10	ENST00000245407.8
MIR3936HG	NR_110997.1	n.73+78G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A5	ENST00000245407.8	c.-207C>G		5_prime_UTR_variant	1/10	1	NM_003060.4	P1
MIR3936HG	ENST00000621103.4	n.73+78G>C		intron_variant, non_coding_transcript_variant		1
MIR3936HG	ENST00000668364.1	n.327+78G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90534 AN: 151872 Hom.: 27771 Cov.: 33

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.596 AC: 262284 AN: 440368 Hom.: 82696 Cov.: 6 AF XY: 0.605 AC XY: 138440 AN XY: 228810

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.857

Gnomad4 FIN exome AF: 0.662

Gnomad4 NFE exome AF: 0.528

Gnomad4 OTH exome AF: 0.581

GnomAD4 genome AF: 0.596 AC: 90608 AN: 151980 Hom.: 27799 Cov.: 33 AF XY: 0.610 AC XY: 45362 AN XY: 74306

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.559

Alfa AF: 0.581 Hom.: 3213

Bravo AF: 0.587

Asia WGS AF: 0.908 AC: 3144 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Renal carnitine transport defect Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

This variant is associated with the following publications: (PMID: 23127916, 16931768, 15107849, 19141711, 22325173, 21279723, 16255050) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	11
Dann	Benign	0.75
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: rs2631367; hg19: chr5-131705458;