rs932845258
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP5_Moderate
The NM_000216.4(ANOS1):c.422G>A(p.Ser141Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,210,028 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )
Consequence
ANOS1
NM_000216.4 missense
NM_000216.4 missense
Scores
2
10
5
Clinical Significance
Conservation
PhyloP100: 3.85
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a domain WAP (size 49) in uniprot entity KALM_HUMAN there are 8 pathogenic changes around while only 2 benign (80%) in NM_000216.4
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-8597153-C-T is Pathogenic according to our data. Variant chrX-8597153-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 431157.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANOS1 | NM_000216.4 | c.422G>A | p.Ser141Asn | missense_variant | 4/14 | ENST00000262648.8 | |
ANOS1 | XM_005274501.5 | c.422G>A | p.Ser141Asn | missense_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANOS1 | ENST00000262648.8 | c.422G>A | p.Ser141Asn | missense_variant | 4/14 | 1 | NM_000216.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000894 AC: 1AN: 111866Hom.: 0 Cov.: 22 AF XY: 0.0000294 AC XY: 1AN XY: 34036
GnomAD3 genomes
?
AF:
AC:
1
AN:
111866
Hom.:
Cov.:
22
AF XY:
AC XY:
1
AN XY:
34036
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000182 AC: 2AN: 1098162Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 363526
GnomAD4 exome
AF:
AC:
2
AN:
1098162
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
363526
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00000894 AC: 1AN: 111866Hom.: 0 Cov.: 22 AF XY: 0.0000294 AC XY: 1AN XY: 34036
GnomAD4 genome
?
AF:
AC:
1
AN:
111866
Hom.:
Cov.:
22
AF XY:
AC XY:
1
AN XY:
34036
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypogonadotropic hypogonadism 1 with or without anosmia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris | Jan 06, 2017 | hypogonadism - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of glycosylation at S141 (P = 0.0013);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at