X-21843311-T-G

Variant names:

• chrX-21843311-T-G
• NM_015884.4:c.217T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015884.4(MBTPS2):​c.217T>G​(p.Tyr73Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: MBTPS2 NM_015884.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBTPS2	NM_015884.4	c.217T>G	p.Tyr73Asp	missense_variant	Exon 2 of 11	ENST00000379484.10	NP_056968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBTPS2	ENST00000379484.10	c.217T>G	p.Tyr73Asp	missense_variant	Exon 2 of 11	1	NM_015884.4	ENSP00000368798.5
MBTPS2	ENST00000365779.2	c.217T>G	p.Tyr73Asp	missense_variant	Exon 2 of 7	1		ENSP00000368796.1
MBTPS2	ENST00000465888.1	n.316T>G		non_coding_transcript_exon_variant	Exon 2 of 6	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.078	T;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.67	T;T
M_CAP	Pathogenic	0.39	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.2	N;N
REVEL	Pathogenic	0.68
Sift	Benign	0.16	T;T
Sift4G	Uncertain	0.025	D;D
Polyphen		0.70	P;P
Vest4		0.64
MutPred		0.50		Loss of MoRF binding (P = 0.0687);Loss of MoRF binding (P = 0.0687);
MVP		1.0
MPC		1.3
ClinPred		0.86	D
GERP RS		5.0
Varity_R		0.34
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-21861429;