rs40357

Positions:

• chr19-54189676-T-C
• chr19-54189676-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000431666.6(MBOAT7):​c.-434A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 153,324 control chromosomes in the GnomAD database, including 4,030 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4012 hom., cov: 34)
  • Exomes 𝑓: 0.16 (18 hom.)
• Consequence: MBOAT7 ENST00000431666.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

Genes affected

MBOAT7 (HGNC:15505): (membrane bound O-acyltransferase domain containing 7) This gene encodes a member of the membrane-bound O-acyltransferases family of integral membrane proteins that have acyltransferase activity. The encoded protein is a lysophosphatidylinositol acyltransferase that has specificity for arachidonoyl-CoA as an acyl donor. This protein is involved in the reacylation of phospholipids as part of the phospholipid remodeling pathway known as the Land cycle. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

TSEN34 (HGNC:15506): (tRNA splicing endonuclease subunit 34) This gene encodes a catalytic subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from precursor tRNAs. The endonuclease complex is also associated with a pre-mRNA 3-prime end processing factor. A mutation in this gene results in the neurological disorder pontocerebellar hypoplasia type 2. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=1.208).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN34	XM_047439391.1	c.-5+80T>C		intron_variant			XP_047295347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBOAT7	ENST00000431666.6	c.-434A>G		5_prime_UTR_variant	1/7	1		ENSP00000410503.2
MBOAT7	ENST00000391754.5	c.-342A>G		upstream_gene_variant		1		ENSP00000375634.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33350 AN: 152106 Hom.: 4004 Cov.: 34

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.155 AC: 171 AN: 1100 Hom.: 18 Cov.: 0 AF XY: 0.150 AC XY: 121 AN XY: 808

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.219 AC: 33380 AN: 152224 Hom.: 4012 Cov.: 34 AF XY: 0.224 AC XY: 16666 AN XY: 74408

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.235

Alfa AF: 0.170 Hom.: 749

Bravo AF: 0.228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs40357; hg19: -;