rs3788987

Variant names:

• chr5-132370597-G-A
• rs3788987
• NM_003060.4:c.393+232G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132370597-G-A
• chr5-132370597-G-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.393+232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0806 in 152,170 control chromosomes in the GnomAD database, including 605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.081 (605 hom., cov: 32)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.67
• Publications: 7 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: Ambry Genetics, ClinGen, G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• 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=-0.85).
• BP6: Variant 5-132370597-G-A is Benign according to our data. Variant chr5-132370597-G-A is described in ClinVar as Benign. ClinVar VariationId is 1292959.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.393+232G>A		intron_variant	Intron 1 of 9	ENST00000245407.8	NP_003051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8	c.393+232G>A		intron_variant	Intron 1 of 9	1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.0806 AC: 12261 AN: 152052 Hom.: 608 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0788

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0806 AC: 12264 AN: 152170 Hom.: 605 Cov.: 32 AF XY: 0.0797 AC XY: 5930 AN XY: 74382

African (AFR) AF: 0.0731 AC: 3033 AN: 41494

American (AMR) AF: 0.0511 AC: 781 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 394 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1386 AN: 5152

South Asian (SAS) AF: 0.0718 AC: 347 AN: 4830

European-Finnish (FIN) AF: 0.0753 AC: 798 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0770 AC: 5240 AN: 68010

Other (OTH) AF: 0.0789 AC: 167 AN: 2116

Alfa AF: 0.0794 Hom.: 70

Bravo AF: 0.0791

Asia WGS AF: 0.129 AC: 448 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.86
PhyloP100		-1.7
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: rs3788987; hg19: chr5-131706289;