rs137852512
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The ENST00000262648.8(ANOS1):c.711G>A(p.Trp237Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
ANOS1
ENST00000262648.8 stop_gained
ENST00000262648.8 stop_gained
Scores
2
2
1
Clinical Significance
Conservation
PhyloP100: 6.70
Genes affected
ANOS1 (HGNC:6211): (anosmin 1) Mutations in this gene cause the X-linked Kallmann syndrome. The encoded protein is similar in sequence to proteins known to function in neural cell adhesion and axonal migration. In addition, this cell surface protein is N-glycosylated and may have anti-protease activity. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-8587809-C-T is Pathogenic according to our data. Variant chrX-8587809-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 10003.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANOS1 | NM_000216.4 | c.711G>A | p.Trp237Ter | stop_gained | 5/14 | ENST00000262648.8 | NP_000207.2 | |
ANOS1 | XM_005274501.5 | c.711G>A | p.Trp237Ter | stop_gained | 5/9 | XP_005274558.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANOS1 | ENST00000262648.8 | c.711G>A | p.Trp237Ter | stop_gained | 5/14 | 1 | NM_000216.4 | ENSP00000262648 | P1 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1088160Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 355290
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
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0
AN:
1088160
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
355290
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 22
GnomAD4 genome
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hypogonadotropic hypogonadism 1 with or without anosmia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 1992 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at