NM_003060.4:c.285T>C

Variant names:

• chr5-132370257-T-C
• rs2631365
• NM_003060.4:c.285T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003060.4(SLC22A5):​c.285T>C​(p.Leu95Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,582,580 control chromosomes in the GnomAD database, including 135,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L95L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.41 (13132 hom., cov: 33)
  • Exomes 𝑓: 0.40 (121958 hom.)
• Consequence: SLC22A5 NM_003060.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.298
• Publications: 28 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 5-132370257-T-C is Benign according to our data. Variant chr5-132370257-T-C is described in ClinVar as Benign. ClinVar VariationId is 94099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.298 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 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.285T>C	p.Leu95Leu	synonymous	Exon 1 of 10	NP_003051.1	O76082-1
	SLC22A5	NM_001308122.2		c.285T>C	p.Leu95Leu	synonymous	Exon 1 of 11	NP_001295051.1	O76082-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	ENST00000245407.8	TSL:1 MANE Select	c.285T>C	p.Leu95Leu	synonymous	Exon 1 of 10	ENSP00000245407.3	O76082-1
	SLC22A5	ENST00000435065.7	TSL:1	c.285T>C	p.Leu95Leu	synonymous	Exon 1 of 11	ENSP00000402760.2	O76082-3
	SLC22A5	ENST00000448810.6	TSL:1	n.285T>C		non_coding_transcript_exon	Exon 1 of 10	ENSP00000401860.2	H7C1R8

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61787 AN: 151952 Hom.: 13124 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.392

GnomAD2 exomes AF: 0.433 AC: 82365 AN: 190330 AF XY: 0.445

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.397

Gnomad EAS exome AF: 0.635

Gnomad FIN exome AF: 0.506

Gnomad NFE exome AF: 0.378

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.405 AC: 579057 AN: 1430510 Hom.: 121958 Cov.: 58 AF XY: 0.412 AC XY: 292033 AN XY: 708786

African (AFR) AF: 0.353 AC: 11583 AN: 32772

American (AMR) AF: 0.324 AC: 12792 AN: 39448

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 10270 AN: 25682

East Asian (EAS) AF: 0.668 AC: 25247 AN: 37786

South Asian (SAS) AF: 0.620 AC: 51246 AN: 82710

European-Finnish (FIN) AF: 0.505 AC: 25053 AN: 49598

Middle Eastern (MID) AF: 0.471 AC: 2689 AN: 5712

European-Non Finnish (NFE) AF: 0.379 AC: 415559 AN: 1097512

Other (OTH) AF: 0.415 AC: 24618 AN: 59290

GnomAD4 genome AF: 0.407 AC: 61825 AN: 152070 Hom.: 13132 Cov.: 33 AF XY: 0.417 AC XY: 31020 AN XY: 74334

African (AFR) AF: 0.359 AC: 14913 AN: 41514

American (AMR) AF: 0.352 AC: 5389 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1444 AN: 3468

East Asian (EAS) AF: 0.668 AC: 3440 AN: 5146

South Asian (SAS) AF: 0.642 AC: 3092 AN: 4816

European-Finnish (FIN) AF: 0.512 AC: 5419 AN: 10588

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26945 AN: 67924

Other (OTH) AF: 0.392 AC: 829 AN: 2114

Alfa AF: 0.366 Hom.: 4306

Bravo AF: 0.386

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	Renal carnitine transport defect (7)
-	-	4	not specified (4)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.6
DANN	Benign	0.74
PhyloP100		-0.30
PromoterAI		0.0037	Neutral
Mutation Taster		=100/0	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: rs2631365; hg19: chr5-131705949; COSMIC: COSV55371662; COSMIC: COSV55371662;