NM_015884.4:c.23_34delTGGTGGTGGTGG

Variant names:

• chrX-21839750-CTGGTGGTGGTGG-C
• rs398124305
• NM_015884.4:c.23_34delTGGTGGTGGTGG

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The NM_015884.4(MBTPS2):​c.23_34delTGGTGGTGGTGG​(p.Val8_Val11del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: MBTPS2 NM_015884.4 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74

Genes affected

MBTPS2 (HGNC:15455): (membrane bound transcription factor peptidase, site 2) This gene encodes a intramembrane zinc metalloprotease, which is essential in development. This protease functions in the signal protein activation involved in sterol control of transcription and the ER stress response. Mutations in this gene have been associated with ichthyosis follicularis with atrichia and photophobia (IFAP syndrome); IFAP syndrome has been quantitatively linked to a reduction in cholesterol homeostasis and ER stress response.[provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_015884.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBTPS2	NM_015884.4	c.23_34delTGGTGGTGGTGG	p.Val8_Val11del	disruptive_inframe_deletion	Exon 1 of 11	ENST00000379484.10	NP_056968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBTPS2	ENST00000379484.10	c.23_34delTGGTGGTGGTGG	p.Val8_Val11del	disruptive_inframe_deletion	Exon 1 of 11	1	NM_015884.4	ENSP00000368798.5
MBTPS2	ENST00000365779.2	c.23_34delTGGTGGTGGTGG	p.Val8_Val11del	disruptive_inframe_deletion	Exon 1 of 7	1		ENSP00000368796.1
MBTPS2	ENST00000465888.1	n.122_133delTGGTGGTGGTGG		non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Nov 20, 2012

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs398124305; hg19: chrX-21857868;