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
• Publications: 2 publications found

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]

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 -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 VariationId is 1140554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 16 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000649993.1. 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
	MIR3936HG	NR_110997.1		n.73+190G>T		intron	N/A
	SLC22A5	NM_003060.4	MANE Select	c.-319C>A		upstream_gene	N/A	NP_003051.1	O76082-1
	SLC22A5	NM_001308122.2		c.-319C>A		upstream_gene	N/A	NP_001295051.1	O76082-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR3936HG	ENST00000621103.4	TSL:1	n.73+190G>T		intron	N/A
	MIR3936HG	ENST00000649993.1		n.6G>T		non_coding_transcript_exon	Exon 1 of 5
	MIR3936HG	ENST00000666504.1		n.50G>T		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.00228 AC: 9 AN: 3954

American (AMR) AF: 0.00345 AC: 13 AN: 3770

Ashkenazi Jewish (ASJ) AF: 0.000197 AC: 1 AN: 5078

East Asian (EAS) AF: 0.00 AC: 0 AN: 12538

South Asian (SAS) AF: 0.00912 AC: 26 AN: 2850

European-Finnish (FIN) AF: 0.0199 AC: 276 AN: 13894

Middle Eastern (MID) AF: 0.00505 AC: 4 AN: 792

European-Non Finnish (NFE) AF: 0.0147 AC: 1441 AN: 97714

Other (OTH) 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

African (AFR) AF: 0.00192 AC: 80 AN: 41578

American (AMR) AF: 0.00301 AC: 46 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4828

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10600

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0136 AC: 923 AN: 67986

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00208 Hom.: 0

Bravo AF: 0.00736

Asia WGS AF: 0.00289 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Renal carnitine transport defect (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.8
DANN	Benign	0.72
PhyloP100		-2.6
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs60978556; hg19: chr5-131705346;