X-8536792-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000216.4(ANOS1):c.1600G>A(p.Val534Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 12445 hom., 17498 hem., cov: 23)

Exomes 𝑓: 0.63 ( 149723 hom. 224115 hem. )

Failed GnomAD Quality Control

Consequence

ANOS1
NM_000216.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.456

Publications

31 publications found

Variant links:

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]

ANOS1 Gene-Disease associations (from GenCC):

hypogonadotropic hypogonadism 1 with or without anosmia
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ANOS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.1132084E-5).

BP6

Variant X-8536792-C-T is Benign according to our data. Variant chrX-8536792-C-T is described in ClinVar as [Benign]. Clinvar id is 255563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANOS1	NM_000216.4 link	c.1600G>A	p.Val534Ile	missense_variant	Exon 11 of 14	ENST00000262648.8	NP_000207.2	P23352

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANOS1	ENST00000262648.8 link	c.1600G>A	p.Val534Ile	missense_variant	Exon 11 of 14	1	NM_000216.4	ENSP00000262648.3		P23352
ANOS1	ENST00000481896.1 link	n.145G>A		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

60238

AN:

110304

Hom.:

12452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.634

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.590

Gnomad MID

AF:

0.600

Gnomad NFE

AF:

0.660

Gnomad OTH

AF:

0.560

GnomAD2 exomes

AF:

0.559

AC:

98770

AN:

176751

AF XY:

0.559

show subpopulations

Gnomad AFR exome

AF:

0.357

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.658

Gnomad EAS exome

AF:

0.655

Gnomad FIN exome

AF:

0.594

Gnomad NFE exome

AF:

0.661

Gnomad OTH exome

AF:

0.600

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.628

AC:

687969

AN:

1094888

Hom.:

149723

Cov.:

AF XY:

0.621

AC XY:

224115

AN XY:

360740

show subpopulations

African (AFR)

AF:

0.350

AC:

9231

AN:

26355

American (AMR)

AF:

0.375

AC:

13084

AN:

34927

Ashkenazi Jewish (ASJ)

AF:

0.653

AC:

12633

AN:

19354

East Asian (EAS)

AF:

0.665

AC:

20037

AN:

30120

South Asian (SAS)

AF:

0.411

AC:

22126

AN:

53790

European-Finnish (FIN)

AF:

0.589

AC:

23803

AN:

40400

Middle Eastern (MID)

AF:

0.567

AC:

2338

AN:

4127

European-Non Finnish (NFE)

AF:

0.663

AC:

556552

AN:

839853

Other (OTH)

AF:

0.613

AC:

28165

AN:

45962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

8459

16918

25377

33836

42295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16552

33104

49656

66208

82760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.546

AC:

60233

AN:

110357

Hom.:

12445

Cov.:

AF XY:

0.536

AC XY:

17498

AN XY:

32647

show subpopulations

African (AFR)

AF:

0.357

AC:

10842

AN:

30405

American (AMR)

AF:

0.474

AC:

4942

AN:

10420

Ashkenazi Jewish (ASJ)

AF:

0.634

AC:

1670

AN:

2634

East Asian (EAS)

AF:

0.653

AC:

2230

AN:

3413

South Asian (SAS)

AF:

0.386

AC:

988

AN:

2561

European-Finnish (FIN)

AF:

0.590

AC:

3421

AN:

5797

Middle Eastern (MID)

AF:

0.610

AC:

130

AN:

213

European-Non Finnish (NFE)

AF:

0.660

AC:

34802

AN:

52751

Other (OTH)

AF:

0.564

AC:

842

AN:

1493

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

944

1889

2833

3778

4722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.561

Hom.:

10531

Bravo

AF:

0.533

TwinsUK

AF:

0.677

AC:

2510

ALSPAC

AF:

0.669

AC:

1932

ESP6500AA

AF:

0.376

AC:

1441

ESP6500EA

AF:

0.671

AC:

4512

ExAC

AF:

0.559

AC:

67769

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jul 27, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Hypogonadotropic hypogonadism 1 with or without anosmia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0030

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.070

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.47

MetaRNN

Benign

0.000031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.090

PhyloP100

-0.46

PrimateAI

Benign

0.27

PROVEAN

Benign

0.23

REVEL

Benign

0.074

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.048

MPC

0.085

ClinPred

0.0025

GERP RS

-4.1

Varity_R

0.027

gMVP

0.084

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over