rs60978556

Variant names:

• chr5-132369654-C-A
• rs60978556
• ENST00000621103.4:n.73+190G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-132369654-C-A
• chr5-132369654-C-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000649993.1(MIR3936HG):​n.6G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 302,636 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (16 hom., cov: 33)
  • Exomes 𝑓: 0.012 (16 hom.)
• Consequence: MIR3936HG ENST00000649993.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.60

Genes affected

MIR3936HG (HGNC:40538): (MIR3936 host gene)

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]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-132369654-C-A is Benign according to our data. Variant chr5-132369654-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1140554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.-319C>A		upstream_gene_variant		ENST00000245407.8	NP_003051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8	c.-319C>A		upstream_gene_variant		1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.00846 AC: 1287 AN: 152136 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.00765

GnomAD4 exome AF: 0.0124 AC: 1871 AN: 150386 Hom.: 16 Cov.: 0 AF XY: 0.0122 AC XY: 930 AN XY: 76182

Gnomad4 AFR exome AF: 0.00228 AC: 9 AN: 3954

Gnomad4 AMR exome AF: 0.00345 AC: 13 AN: 3770

Gnomad4 ASJ exome AF: 0.000197 AC: 1 AN: 5078

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 12538

Gnomad4 SAS exome AF: 0.00912 AC: 26 AN: 2850

Gnomad4 FIN exome AF: 0.0199 AC: 276 AN: 13894

Gnomad4 NFE exome AF: 0.0147 AC: 1441 AN: 97714

Gnomad4 Remaining exome AF: 0.0103 AC: 101 AN: 9796

GnomAD4 genome AF: 0.00844 AC: 1285 AN: 152250 Hom.: 16 Cov.: 33 AF XY: 0.00822 AC XY: 612 AN XY: 74456

Gnomad4 AFR AF: 0.00192 AC: 0.00192409 AN: 0.00192409

Gnomad4 AMR AF: 0.00301 AC: 0.00300772 AN: 0.00300772

Gnomad4 ASJ AF: 0.000865 AC: 0.000864553 AN: 0.000864553

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00518 AC: 0.00517813 AN: 0.00517813

Gnomad4 FIN AF: 0.0179 AC: 0.0179245 AN: 0.0179245

Gnomad4 NFE AF: 0.0136 AC: 0.0135763 AN: 0.0135763

Gnomad4 OTH AF: 0.00757 AC: 0.00756859 AN: 0.00756859

Alfa AF: 0.00208 Hom.: 0

Bravo AF: 0.00736

Asia WGS AF: 0.00289 AC: 12 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Renal carnitine transport defect Benign:2

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 19, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.8
DANN	Benign	0.72
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60978556; hg19: chr5-131705346;