chr16-84054442-C-T

Variant names:

• chr16-84054442-C-T
• rs11607
• NM_003791.4:c.*7G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.48
• Publications: 15 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: Benign. The variant received -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 VariationId 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.

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.*7G>A		3_prime_UTR	Exon 23 of 23	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.*7G>A		3_prime_UTR	Exon 23 of 23	ENSP00000344223.3	Q14703
	MBTPS1	ENST00000851026.1		c.*7G>A		3_prime_UTR	Exon 23 of 23	ENSP00000521095.1
	MBTPS1	ENST00000562886.1	TSL:2	n.2665G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53113 AN: 152102 Hom.: 9417 Cov.: 34

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

GnomAD2 exomes AF: 0.367 AC: 84277 AN: 229660 AF XY: 0.361

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 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.: 33 AF XY: 0.343 AC XY: 243618 AN XY: 709806

African (AFR) AF: 0.318 AC: 10399 AN: 32724

American (AMR) AF: 0.488 AC: 20593 AN: 42174

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 10003 AN: 24296

East Asian (EAS) AF: 0.428 AC: 16729 AN: 39064

South Asian (SAS) AF: 0.299 AC: 24684 AN: 82624

European-Finnish (FIN) AF: 0.360 AC: 18580 AN: 51542

Middle Eastern (MID) AF: 0.396 AC: 2234 AN: 5638

European-Non Finnish (NFE) AF: 0.338 AC: 370769 AN: 1095526

Other (OTH) AF: 0.352 AC: 20756 AN: 59018

GnomAD4 genome AF: 0.349 AC: 53177 AN: 152220 Hom.: 9439 Cov.: 34 AF XY: 0.352 AC XY: 26171 AN XY: 74444

African (AFR) AF: 0.324 AC: 13446 AN: 41540

American (AMR) AF: 0.435 AC: 6657 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1422 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2146 AN: 5178

South Asian (SAS) AF: 0.315 AC: 1519 AN: 4828

European-Finnish (FIN) AF: 0.360 AC: 3821 AN: 10602

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22761 AN: 67990

Other (OTH) AF: 0.370 AC: 783 AN: 2114

Alfa AF: 0.346 Hom.: 32640

Bravo AF: 0.359

Asia WGS AF: 0.349 AC: 1214 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MBTPS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.3
DANN	Benign	0.87
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs11607; hg19: chr16-84088047; COSMIC: COSV58569999; COSMIC: COSV58569999;