X-21839750-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_015884.4(MBTPS2):c.16C>T(p.Leu6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,077,163 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000019 ( 0 hom. 1 hem. )
Consequence
MBTPS2
NM_015884.4 synonymous
NM_015884.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.700
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant X-21839750-C-T is Benign according to our data. Variant chrX-21839750-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2974115.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.7 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MBTPS2 | NM_015884.4 | c.16C>T | p.Leu6= | synonymous_variant | 1/11 | ENST00000379484.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MBTPS2 | ENST00000379484.10 | c.16C>T | p.Leu6= | synonymous_variant | 1/11 | 1 | NM_015884.4 | P1 | |
MBTPS2 | ENST00000365779.2 | c.16C>T | p.Leu6= | synonymous_variant | 1/7 | 1 | |||
MBTPS2 | ENST00000465888.1 | n.115C>T | non_coding_transcript_exon_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
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23
GnomAD3 exomes AF: 0.00000729 AC: 1AN: 137139Hom.: 0 AF XY: 0.0000238 AC XY: 1AN XY: 42043
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GnomAD4 exome AF: 0.00000186 AC: 2AN: 1077163Hom.: 0 Cov.: 30 AF XY: 0.00000285 AC XY: 1AN XY: 350855
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GnomAD4 genome Cov.: 23
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 21, 2023 | - - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at