Genetic Variant MBTPS1:c.2963-17C>T (chr16-84054662-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003791.4(MBTPS1):c.2963-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 1,558,546 control chromosomes in the GnomAD database, including 4,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 614 hom., cov: 33)

Exomes 𝑓: 0.064 ( 3680 hom. )

Consequence

MBTPS1
NM_003791.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.347

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-84054662-G-A is Benign according to our data. Variant chr16-84054662-G-A is described in ClinVar as [Benign]. Clinvar id is 1600366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBTPS1	NM_003791.4 link	c.2963-17C>T	intron_variant	Intron 22 of 22	ENST00000343411.8	NP_003782.1	Q14703
MBTPS1	XM_047434830.1 link	c.2963-17C>T	intron_variant	Intron 22 of 22		XP_047290786.1
MBTPS1	XM_047434831.1 link	c.2963-17C>T	intron_variant	Intron 22 of 22		XP_047290787.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MBTPS1	ENST00000343411.8 link	c.2963-17C>T	intron_variant	Intron 22 of 22	1	NM_003791.4	ENSP00000344223.3	Q14703
MBTPS1	ENST00000562886.1 link	n.2462-17C>T	intron_variant	Intron 2 of 2	2
MBTPS1	ENST00000562906.2 link	n.2041-17C>T	intron_variant	Intron 1 of 1	2
MBTPS1	ENST00000570064.5 link	n.2207-17C>T	intron_variant	Intron 11 of 11	2

Frequencies

GnomAD3 genomes

AF:

0.0814

AC:

12392

AN:

152180

Hom.:

614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0654

Gnomad ASJ

AF:

0.0941

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.0915

Gnomad FIN

AF:

0.0431

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0548

Gnomad OTH

AF:

0.0913

GnomAD3 exomes

AF:

0.0816

AC:

17033

AN:

208848

Hom.:

991

AF XY:

0.0797

AC XY:

9034

AN XY:

113320

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.0623

Gnomad ASJ exome

AF:

0.0980

Gnomad EAS exome

AF:

0.247

Gnomad SAS exome

AF:

0.0849

Gnomad FIN exome

AF:

0.0421

Gnomad NFE exome

AF:

0.0598

Gnomad OTH exome

AF:

0.0744

GnomAD4 exome

AF:

0.0635

AC:

89304

AN:

1406248

Hom.:

3680

Cov.:

AF XY:

0.0642

AC XY:

44622

AN XY:

694804

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.0598

Gnomad4 ASJ exome

AF:

0.0934

Gnomad4 EAS exome

AF:

0.230

Gnomad4 SAS exome

AF:

0.0849

Gnomad4 FIN exome

AF:

0.0420

Gnomad4 NFE exome

AF:

0.0540

Gnomad4 OTH exome

AF:

0.0786

GnomAD4 genome

AF:

0.0814

AC:

12401

AN:

152298

Hom.:

614

Cov.:

AF XY:

0.0816

AC XY:

6075

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.0654

Gnomad4 ASJ

AF:

0.0941

Gnomad4 EAS

AF:

0.248

Gnomad4 SAS

AF:

0.0913

Gnomad4 FIN

AF:

0.0431

Gnomad4 NFE

AF:

0.0548

Gnomad4 OTH

AF:

0.0922

Alfa

AF:

0.0738

Hom.:

Bravo

AF:

0.0860

Asia WGS

AF:

0.158

AC:

546

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.28

DANN

Benign

0.31

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