NM_000216.4(ANOS1):c.1369C>T (p.Arg457Ter) AND Hypogonadotropic hypogonadism 1 with or without anosmia

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 27, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001850175.5

Allele description

NM_000216.4(ANOS1):c.1369C>T (p.Arg457Ter)

Gene:

ANOS1:anosmin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp22.31

Genomic location:

Preferred name:

NM_000216.4(ANOS1):c.1369C>T (p.Arg457Ter)

HGVS:

NC_000023.11:g.8539744G>A
NG_007088.2:g.197443C>T
NM_000216.4:c.1369C>TMANE SELECT
NP_000207.2:p.Arg457Ter
NC_000023.10:g.8507785G>A
NG_007088.1:g.197443C>T
NM_000216.2:c.1369C>T

Protein change:

R457*

Links:

dbSNP: rs727505374

NCBI 1000 Genomes Browser:

rs727505374

Molecular consequence:

NM_000216.4:c.1369C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Hypogonadotropic hypogonadism 1 with or without anosmia (HH1)
Synonyms:: Kallmann syndrome 1; Kallmann syndrome, X-linked; Kallmann syndrome, type 1, X-linked; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010635; MedGen: C1563719; Orphanet: 478; OMIM: 308700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002120638	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 2, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23643382, 8504298, 11297579, 28492532
SCV004171063	Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	criteria provided, single submitter (Hauer et al. (Genet Med. 2018))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002120638

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 2, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004171063

Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

criteria provided, single submitter

(Hauer et al. (Genet Med. 2018))

Pathogenic
(Nov 27, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.

Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, et al.

Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008.

PubMed [citation]

PMID:: 23643382
PMCID:: PMC3644636

Heterogeneity in the mutations responsible for X chromosome-linked Kallmann syndrome.

Hardelin JP, Levilliers J, Blanchard S, Carel JC, Leutenegger M, Pinard-Bertelletto JP, Bouloux P, Petit C.

Hum Mol Genet. 1993 Apr;2(4):373-7.

PubMed [citation]

PMID:: 8504298

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002120638.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with Kallman syndrome (PMID: 11297579, 23643382). ClinVar contains an entry for this variant (Variation ID: 180157). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg457*) in the ANOS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANOS1 are known to be pathogenic (PMID: 8504298, 11297579).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, SCV004171063.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

Description

This variant has been identified by standard clinical testing. Selected ACMG criteria: Pathogenic (I):PM2;PS2;PVS1

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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