Variant X-21843225-G-C 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.131G>C(p.Ser44Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,095,503 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.000011 ( 0 hom. 2 hem. )

Consequence

MBTPS2
NM_015884.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.65

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.082437426).

BP6

Variant X-21843225-G-C is Benign according to our data. Variant chrX-21843225-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3293581.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBTPS2	NM_015884.4 linkuse as main transcript	c.131G>C	p.Ser44Thr	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.131G>C	p.Ser44Thr	missense_variant	2/11	1	NM_015884.4	P1
MBTPS2	ENST00000365779.2 linkuse as main transcript	c.131G>C	p.Ser44Thr	missense_variant	2/7	1
MBTPS2	ENST00000465888.1 linkuse as main transcript	n.230G>C		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

183511

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67943

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000216

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1095503

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

360899

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000107

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.029

T;T

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.082

T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.50

N;N

REVEL

Benign

0.24

Sift

Benign

0.89

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.010

B;B

Vest4

0.13

MutPred

0.54

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);

MVP

0.50

MPC

0.59

ClinPred

0.044

GERP RS

4.6

Varity_R

0.15

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over