16-84055994-C-A

Variant names:

• chr16-84055994-C-A
• rs372285651
• NM_003791.4:c.2962+11G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003791.4(MBTPS1):​c.2962+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,698 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MBTPS1 NM_003791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• spondyloepiphyseal dysplasia, kondo-fu type

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003791.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBTPS1	NM_003791.4	MANE Select	c.2962+11G>T		intron	N/A	NP_003782.1	Q14703

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBTPS1	ENST00000343411.8	TSL:1 MANE Select	c.2962+11G>T		intron	N/A	ENSP00000344223.3	Q14703
	MBTPS1	ENST00000851026.1		c.2962+11G>T		intron	N/A	ENSP00000521095.1
	MBTPS1	ENST00000562886.1	TSL:2	n.2461+11G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250606 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455698 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723048

African (AFR) AF: 0.00 AC: 0 AN: 33350

American (AMR) AF: 0.0000225 AC: 1 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39484

South Asian (SAS) AF: 0.00 AC: 0 AN: 85984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4786

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108020

Other (OTH) AF: 0.00 AC: 0 AN: 60092

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.031
DANN	Benign	0.58
PhyloP100		-1.7

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

Other links and lift over

dbSNP: rs372285651; hg19: chr16-84089599;