ENST00000621103.4:n.73+270C>G

Variant names:

• chr5-132369574-G-C
• rs2631369
• ENST00000621103.4:n.73+270C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000621103.4(MIR3936HG):​n.73+270C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 184,386 control chromosomes in the GnomAD database, including 9,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8146 hom., cov: 32)
  • Exomes 𝑓: 0.31 (1661 hom.)
• Consequence: MIR3936HG ENST00000621103.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.116
• Publications: 15 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: 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=-0.83).
• BP6: Variant 5-132369574-G-C is Benign according to our data. Variant chr5-132369574-G-C is described in ClinVar as Benign. ClinVar VariationId is 1221263.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.-399G>C		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.-399G>C		upstream_gene_variant		1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48676 AN: 151904 Hom.: 8142 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.309 AC: 10002 AN: 32364 Hom.: 1661 Cov.: 0 AF XY: 0.306 AC XY: 5061 AN XY: 16528

African (AFR) AF: 0.270 AC: 310 AN: 1148

American (AMR) AF: 0.265 AC: 200 AN: 756

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 326 AN: 1120

East Asian (EAS) AF: 0.346 AC: 783 AN: 2262

South Asian (SAS) AF: 0.561 AC: 175 AN: 312

European-Finnish (FIN) AF: 0.407 AC: 1191 AN: 2928

Middle Eastern (MID) AF: 0.393 AC: 70 AN: 178

European-Non Finnish (NFE) AF: 0.291 AC: 6251 AN: 21484

Other (OTH) AF: 0.320 AC: 696 AN: 2176

GnomAD4 genome AF: 0.320 AC: 48707 AN: 152022 Hom.: 8146 Cov.: 32 AF XY: 0.332 AC XY: 24630 AN XY: 74296

African (AFR) AF: 0.284 AC: 11804 AN: 41492

American (AMR) AF: 0.299 AC: 4576 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1048 AN: 3466

East Asian (EAS) AF: 0.380 AC: 1951 AN: 5140

South Asian (SAS) AF: 0.562 AC: 2706 AN: 4816

European-Finnish (FIN) AF: 0.431 AC: 4543 AN: 10552

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21192 AN: 67940

Other (OTH) AF: 0.308 AC: 649 AN: 2110

Alfa AF: 0.214 Hom.: 535

Bravo AF: 0.302

Asia WGS AF: 0.477 AC: 1656 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 23, 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	-0.83
CADD	Benign	4.5
DANN	Benign	0.63
PhyloP100		-0.12
PromoterAI		0.024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2631369; hg19: chr5-131705266;