5-132369605-T-G

Variant names:

• chr5-132369605-T-G
• rs2631368
• ENST00000621103.4:n.73+239A>C

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+239A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 212,720 control chromosomes in the GnomAD database, including 11,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8122 hom., cov: 33)
  • Exomes 𝑓: 0.32 (3151 hom.)
• Consequence: MIR3936HG ENST00000621103.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35
• Publications: 13 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=-0.81).
• BP6: Variant 5-132369605-T-G is Benign according to our data. Variant chr5-132369605-T-G is described in ClinVar as Benign. ClinVar VariationId is 1266598.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.-368T>G		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.-368T>G		upstream_gene_variant		1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48627 AN: 151904 Hom.: 8118 Cov.: 33

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.316 AC: 19153 AN: 60698 Hom.: 3151 Cov.: 0 AF XY: 0.312 AC XY: 9673 AN XY: 30972

African (AFR) AF: 0.278 AC: 543 AN: 1954

American (AMR) AF: 0.284 AC: 424 AN: 1494

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 637 AN: 2132

East Asian (EAS) AF: 0.356 AC: 1691 AN: 4756

South Asian (SAS) AF: 0.559 AC: 360 AN: 644

European-Finnish (FIN) AF: 0.416 AC: 2441 AN: 5870

Middle Eastern (MID) AF: 0.414 AC: 140 AN: 338

European-Non Finnish (NFE) AF: 0.294 AC: 11649 AN: 39564

Other (OTH) AF: 0.321 AC: 1268 AN: 3946

GnomAD4 genome AF: 0.320 AC: 48658 AN: 152022 Hom.: 8122 Cov.: 33 AF XY: 0.331 AC XY: 24613 AN XY: 74290

African (AFR) AF: 0.284 AC: 11795 AN: 41490

American (AMR) AF: 0.299 AC: 4575 AN: 15298

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

East Asian (EAS) AF: 0.379 AC: 1944 AN: 5126

South Asian (SAS) AF: 0.562 AC: 2711 AN: 4824

European-Finnish (FIN) AF: 0.429 AC: 4530 AN: 10566

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.312 AC: 21169 AN: 67942

Other (OTH) AF: 0.308 AC: 649 AN: 2108

Alfa AF: 0.320 Hom.: 1300

Bravo AF: 0.302

Asia WGS AF: 0.476 AC: 1654 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	-0.81
CADD	Benign	0.77
DANN	Benign	0.54
PhyloP100		-1.4
PromoterAI		-0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Other links and lift over

dbSNP: rs2631368; hg19: chr5-131705297;