5-132369895-C-T

Variant names:

• chr5-132369895-C-T
• rs13180043
• NM_003060.4:c.-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 VariationId 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.

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.-78C>T		5_prime_UTR	Exon 1 of 10	NP_003051.1
	SLC22A5	NM_001308122.2		c.-78C>T		5_prime_UTR	Exon 1 of 11	NP_001295051.1
	MIR3936HG	NR_110997.1		n.22G>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.-78C>T		5_prime_UTR	Exon 1 of 10	ENSP00000245407.3
	SLC22A5	ENST00000435065.7	TSL:1	c.-78C>T		5_prime_UTR	Exon 1 of 11	ENSP00000402760.2
	SLC22A5	ENST00000448810.6	TSL:1	n.-78C>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000401860.2

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Renal carnitine transport defect (3)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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;