5-132389258-T-C

Variant names:

• chr5-132389258-T-C
• rs274554
• NM_003060.4:c.1052+237T>C

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.1052+237T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 493,902 control chromosomes in the GnomAD database, including 165,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (44808 hom., cov: 32)
  • Exomes 𝑓: 0.84 (121017 hom.)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06
• Publications: 22 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]

SLC22A5 Gene-Disease associations (from GenCC):

• systemic primary carnitine deficiency disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet, G2P, ClinGen
• short QT syndrome

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-132389258-T-C is Benign according to our data. Variant chr5-132389258-T-C is described in ClinVar as Benign. ClinVar VariationId is 670106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 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.1052+237T>C		intron	N/A	NP_003051.1	O76082-1
	SLC22A5	NM_001308122.2		c.1124+237T>C		intron	N/A	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.1052+237T>C		intron	N/A	ENSP00000245407.3	O76082-1
	SLC22A5	ENST00000435065.7	TSL:1	c.1124+237T>C		intron	N/A	ENSP00000402760.2	O76082-3
	SLC22A5	ENST00000448810.6	TSL:1	n.1052+237T>C		intron	N/A	ENSP00000401860.2	H7C1R8

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114381 AN: 152004 Hom.: 44808 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.789

GnomAD4 exome AF: 0.839 AC: 286681 AN: 341780 Hom.: 121017 Cov.: 2 AF XY: 0.840 AC XY: 154435 AN XY: 183954

African (AFR) AF: 0.513 AC: 5023 AN: 9784

American (AMR) AF: 0.815 AC: 13270 AN: 16290

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 8921 AN: 10150

East Asian (EAS) AF: 0.931 AC: 19473 AN: 20906

South Asian (SAS) AF: 0.825 AC: 36693 AN: 44496

European-Finnish (FIN) AF: 0.871 AC: 16094 AN: 18486

Middle Eastern (MID) AF: 0.769 AC: 1078 AN: 1402

European-Non Finnish (NFE) AF: 0.847 AC: 170511 AN: 201400

Other (OTH) AF: 0.828 AC: 15618 AN: 18866

GnomAD4 genome AF: 0.752 AC: 114411 AN: 152122 Hom.: 44808 Cov.: 32 AF XY: 0.756 AC XY: 56240 AN XY: 74386

African (AFR) AF: 0.508 AC: 21069 AN: 41448

American (AMR) AF: 0.810 AC: 12396 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3019 AN: 3472

East Asian (EAS) AF: 0.910 AC: 4715 AN: 5180

South Asian (SAS) AF: 0.832 AC: 4010 AN: 4818

European-Finnish (FIN) AF: 0.869 AC: 9217 AN: 10602

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57341 AN: 67984

Other (OTH) AF: 0.783 AC: 1652 AN: 2110

Alfa AF: 0.813 Hom.: 82987

Bravo AF: 0.739

Asia WGS AF: 0.805 AC: 2796 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.39
PhyloP100		-1.1
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: rs274554; hg19: chr5-131724950;