rs139020486

Variant names:

• chrX-21839764-G-A
• rs139020486
• NM_015884.4:c.30G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-21839764-G-A
• chrX-21839764-G-C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015884.4(MBTPS2):​c.30G>A​(p.Val10Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V10V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: MBTPS2 NM_015884.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• keratosis follicularis spinulosa decalvans

  Inheritance: AD, XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• IFAP syndrome 1, with or without BRESHECK syndrome

  Inheritance: XL, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Olmsted syndrome, X-linked

  Inheritance: XL Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P
• osteogenesis imperfecta, type 19

  Inheritance: XL Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• mutilating palmoplantar keratoderma with periorificial keratotic plaques

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• BRESEK syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• keratosis follicularis spinulosa decalvans, X-linked

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000304431 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=2.44 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015884.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBTPS2	NM_015884.4	MANE Select	c.30G>A	p.Val10Val	synonymous	Exon 1 of 11	NP_056968.1	O43462

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBTPS2	ENST00000379484.10	TSL:1 MANE Select	c.30G>A	p.Val10Val	synonymous	Exon 1 of 11	ENSP00000368798.5	O43462
	MBTPS2	ENST00000365779.2	TSL:1	c.30G>A	p.Val10Val	synonymous	Exon 1 of 7	ENSP00000368796.1	B9ZVQ3
	MBTPS2	ENST00000860794.1		c.30G>A	p.Val10Val	synonymous	Exon 1 of 12	ENSP00000530853.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00 AC: 0 AN: 145958 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.6
DANN	Benign	0.93
PhyloP100		2.4
PromoterAI		-0.0070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Other links and lift over

dbSNP: rs139020486; hg19: chrX-21857882;