X-21842842-G-C

Position:

• chrX-21842842-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015884.4(MBTPS2):​c.76-328G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 109,885 control chromosomes in the GnomAD database, including 8,131 homozygotes. There are 14,181 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (8131 hom., 14181 hem., cov: 22)
• Consequence: MBTPS2 NM_015884.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.167

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant X-21842842-G-C is Benign according to our data. Variant chrX-21842842-G-C is described in ClinVar as [Benign]. Clinvar id is 1234939.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBTPS2	NM_015884.4	c.76-328G>C		intron_variant		ENST00000379484.10	NP_056968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBTPS2	ENST00000379484.10	c.76-328G>C		intron_variant		1	NM_015884.4	ENSP00000368798.5
MBTPS2	ENST00000365779.2	c.76-328G>C		intron_variant		1		ENSP00000368796.1
MBTPS2	ENST00000465888.1	n.175-328G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.445 AC: 48894 AN: 109834 Hom.: 8128 Cov.: 22 AF XY: 0.440 AC XY: 14134 AN XY: 32126

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.445 AC: 48944 AN: 109885 Hom.: 8131 Cov.: 22 AF XY: 0.441 AC XY: 14181 AN XY: 32187

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.452

Alfa AF: 0.420 Hom.: 2853

Bravo AF: 0.465

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.60
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs6528056; hg19: chrX-21860960;