chr5-132369866-G-T

Variant names:

• chr5-132369866-G-T
• rs13180186
• NM_003060.4:c.-107G>T

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.-107G>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 0.0803 in 1,456,946 control chromosomes in the GnomAD database, including 5,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.077 (578 hom., cov: 33)
  • Exomes 𝑓: 0.081 (5359 hom.)
• Consequence: SLC22A5 NM_003060.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 5-132369866-G-T is Benign according to our data. Variant chr5-132369866-G-T is described in ClinVar as Benign. ClinVar VariationId is 350809.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.

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.-107G>T		5_prime_UTR	Exon 1 of 10	NP_003051.1	O76082-1
	SLC22A5	NM_001308122.2		c.-107G>T		5_prime_UTR	Exon 1 of 11	NP_001295051.1	O76082-3
	MIR3936HG	NR_110997.1		n.51C>A		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	ENST00000245407.8	TSL:1 MANE Select	c.-107G>T		5_prime_UTR	Exon 1 of 10	ENSP00000245407.3	O76082-1
	SLC22A5	ENST00000435065.7	TSL:1	c.-107G>T		5_prime_UTR	Exon 1 of 11	ENSP00000402760.2	O76082-3
	SLC22A5	ENST00000448810.6	TSL:1	n.-107G>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000401860.2	H7C1R8

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11687 AN: 152106 Hom.: 582 Cov.: 33

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.0647

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.0760

GnomAD4 exome AF: 0.0807 AC: 105257 AN: 1304728 Hom.: 5359 Cov.: 21 AF XY: 0.0802 AC XY: 51663 AN XY: 644316

African (AFR) AF: 0.0604 AC: 1795 AN: 29738

American (AMR) AF: 0.0409 AC: 1201 AN: 29396

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 2432 AN: 20756

East Asian (EAS) AF: 0.297 AC: 10929 AN: 36798

South Asian (SAS) AF: 0.0550 AC: 3878 AN: 70516

European-Finnish (FIN) AF: 0.0767 AC: 2894 AN: 37752

Middle Eastern (MID) AF: 0.0669 AC: 253 AN: 3784

European-Non Finnish (NFE) AF: 0.0757 AC: 77329 AN: 1021504

Other (OTH) AF: 0.0834 AC: 4546 AN: 54484

GnomAD4 genome AF: 0.0768 AC: 11685 AN: 152218 Hom.: 578 Cov.: 33 AF XY: 0.0759 AC XY: 5645 AN XY: 74406

African (AFR) AF: 0.0617 AC: 2565 AN: 41562

American (AMR) AF: 0.0493 AC: 755 AN: 15300

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

East Asian (EAS) AF: 0.269 AC: 1384 AN: 5148

South Asian (SAS) AF: 0.0646 AC: 312 AN: 4830

European-Finnish (FIN) AF: 0.0753 AC: 798 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0767 AC: 5215 AN: 67986

Other (OTH) AF: 0.0762 AC: 161 AN: 2114

Alfa AF: 0.0764 Hom.: 64

Bravo AF: 0.0746

Asia WGS AF: 0.123 AC: 428 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

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	-0.77
CADD	Benign	0.47
DANN	Benign	0.52
PhyloP100		-1.6
PromoterAI		-0.0062	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13180186; hg19: chr5-131705558;