Variant X-21843311-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_015884.4(MBTPS2):c.217T>A(p.Tyr73Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000645 in 1,208,872 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y73C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000070 ( 0 hom. 32 hem. )

Consequence

MBTPS2
NM_015884.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.98

Variant links:

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]

MBTPS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18895727).

BP6

Variant X-21843311-T-A is Benign according to our data. Variant chrX-21843311-T-A is described in ClinVar as [Benign]. Clinvar id is 1601559.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 32 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBTPS2	NM_015884.4 linkuse as main transcript	c.217T>A	p.Tyr73Asn	missense_variant	2/11	ENST00000379484.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MBTPS2	ENST00000379484.10 linkuse as main transcript	c.217T>A	p.Tyr73Asn	missense_variant	2/11	1	NM_015884.4	P1
MBTPS2	ENST00000365779.2 linkuse as main transcript	c.217T>A	p.Tyr73Asn	missense_variant	2/7	1
MBTPS2	ENST00000465888.1 linkuse as main transcript	n.316T>A		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes

AF:

0.00000891

AC:

AN:

112178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34318

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000709

AC:

AN:

183385

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

67827

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000577

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000702

AC:

AN:

1096694

Hom.:

Cov.:

AF XY:

0.0000884

AC XY:

AN XY:

362068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000758

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000393

Gnomad4 OTH exome

AF:

0.0000652

GnomAD4 genome

AF:

0.00000891

AC:

AN:

112178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.39

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.048

T;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.86

D;D

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.19

T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.51

N;N

REVEL

Uncertain

0.54

Sift

Benign

0.30

T;T

Sift4G

Uncertain

0.046

D;T

Polyphen

0.085

B;B

Vest4

0.42

MVP

1.0

MPC

1.0

ClinPred

0.085

GERP RS

5.0

Varity_R

0.23

gMVP

0.94

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