Genetic Variant MBTPS1:c.*7G>A (chr16-84054442-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003791.4(MBTPS1):c.*7G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,584,826 control chromosomes in the GnomAD database, including 96,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.35 ( 9439 hom., cov: 34)

Exomes 𝑓: 0.35 ( 86914 hom. )

Consequence

MBTPS1
NM_003791.4 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.48

Variant links:

Genes affected

MBTPS1 (HGNC:15456): (membrane bound transcription factor peptidase, site 1) This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to the cis/medial-Golgi where a second autocatalytic event takes place and the catalytic activity is acquired. It encodes a type 1 membrane bound protease which is ubiquitously expressed and regulates cholesterol or lipid homeostasis via cleavage of substrates at non-basic residues. Mutations in this gene may be associated with lysosomal dysfunction. [provided by RefSeq, Feb 2014]

MBTPS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 16-84054442-C-T is Benign according to our data. Variant chr16-84054442-C-T is described in ClinVar as [Benign]. Clinvar id is 3060449.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBTPS1	NM_003791.4 link	c.*7G>A	3_prime_UTR_variant	Exon 23 of 23	ENST00000343411.8	NP_003782.1	Q14703
MBTPS1	XM_047434830.1 link	c.*7G>A	3_prime_UTR_variant	Exon 23 of 23		XP_047290786.1
MBTPS1	XM_047434831.1 link	c.*7G>A	3_prime_UTR_variant	Exon 23 of 23		XP_047290787.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MBTPS1	ENST00000343411 link	c.*7G>A	3_prime_UTR_variant	Exon 23 of 23	1	NM_003791.4	ENSP00000344223.3	Q14703
MBTPS1	ENST00000562886.1 link	n.2665G>A	non_coding_transcript_exon_variant	Exon 3 of 3	2
MBTPS1	ENST00000562906.2 link	n.2244G>A	non_coding_transcript_exon_variant	Exon 2 of 2	2
MBTPS1	ENST00000570064.5 link	n.2410G>A	non_coding_transcript_exon_variant	Exon 12 of 12	2

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53113

AN:

152102

Hom.:

9417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.313

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.367

AC:

84277

AN:

229660

Hom.:

16005

AF XY:

0.361

AC XY:

44663

AN XY:

123880

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.497

Gnomad ASJ exome

AF:

0.409

Gnomad EAS exome

AF:

0.424

Gnomad SAS exome

AF:

0.302

Gnomad FIN exome

AF:

0.360

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.379

GnomAD4 exome

AF:

0.345

AC:

494747

AN:

1432606

Hom.:

86914

Cov.:

AF XY:

0.343

AC XY:

243618

AN XY:

709806

show subpopulations

Gnomad4 AFR exome

AF:

0.318

Gnomad4 AMR exome

AF:

0.488

Gnomad4 ASJ exome

AF:

0.412

Gnomad4 EAS exome

AF:

0.428

Gnomad4 SAS exome

AF:

0.299

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.338

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

AF:

0.349

AC:

53177

AN:

152220

Hom.:

9439

Cov.:

AF XY:

0.352

AC XY:

26171

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.324

Gnomad4 AMR

AF:

0.435

Gnomad4 ASJ

AF:

0.410

Gnomad4 EAS

AF:

0.414

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.360

Gnomad4 NFE

AF:

0.335

Gnomad4 OTH

AF:

0.370

Alfa

AF:

0.348

Hom.:

13502

Bravo

AF:

0.359

Asia WGS

AF:

0.349

AC:

1214

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MBTPS1-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.3

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over