chrX-8536792-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chrX-8536792-C-T is described in Lovd as [Benign]. Variant chrX-8536792-C-T is described in Lovd as [Likely_benign].

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.:

AF XY:

0.537

AC XY:

17484

AN XY:

32584

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

GnomAD3 exomes

AF:

0.559

AC:

98770

AN:

176751

Hom.:

19112

AF XY:

0.559

AC XY:

34599

AN XY:

61855

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 SAS exome

AF:

0.408

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

Gnomad4 AFR exome

AF:

0.350

Gnomad4 AMR exome

AF:

0.375

Gnomad4 ASJ exome

AF:

0.653

Gnomad4 EAS exome

AF:

0.665

Gnomad4 SAS exome

AF:

0.411

Gnomad4 FIN exome

AF:

0.589

Gnomad4 NFE exome

AF:

0.663

Gnomad4 OTH exome

AF:

0.613

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

Gnomad4 AFR

AF:

0.357

Gnomad4 AMR

AF:

0.474

Gnomad4 ASJ

AF:

0.634

Gnomad4 EAS

AF:

0.653

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.590

Gnomad4 NFE

AF:

0.660

Gnomad4 OTH

AF:

0.564

Alfa

AF:

0.599

Hom.:

8719

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

- -

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

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over