X-8536860-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000216.4(ANOS1):c.1532C>A(p.Ser511Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,205,846 control chromosomes in the GnomAD database, including 4 homozygotes. There are 713 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., 32 hem., cov: 22)

Exomes 𝑓: 0.0017 ( 4 hom. 681 hem. )

Consequence

ANOS1
NM_000216.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:5

Conservation

PhyloP100: 2.50

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012378961).

BP6

Variant X-8536860-G-T is Benign according to our data. Variant chrX-8536860-G-T is described in ClinVar as [Benign]. Clinvar id is 463525.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-8536860-G-T is described in Lovd as [Likely_benign]. Variant chrX-8536860-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00106 (118/111661) while in subpopulation SAS AF= 0.00227 (6/2644). AF 95% confidence interval is 0.00143. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 32 XL,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANOS1	NM_000216.4 link	c.1532C>A	p.Ser511Tyr	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.1532C>A	p.Ser511Tyr	missense_variant	Exon 11 of 14	1	NM_000216.4	ENSP00000262648.3		P23352
ANOS1	ENST00000481896.1 link	n.77C>A		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

118

AN:

111609

Hom.:

Cov.:

AF XY:

0.000947

AC XY:

AN XY:

33795

show subpopulations

Gnomad AFR

AF:

0.000196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00226

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00171

Gnomad OTH

AF:

0.000666

GnomAD3 exomes

AF:

0.00149

AC:

271

AN:

181586

Hom.:

AF XY:

0.00200

AC XY:

132

AN XY:

66106

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.000512

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00278

Gnomad FIN exome

AF:

0.0000628

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00173

AC:

1892

AN:

1094185

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

681

AN XY:

359629

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000682

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00273

Gnomad4 FIN exome

AF:

0.000123

Gnomad4 NFE exome

AF:

0.00192

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00106

AC:

118

AN:

111661

Hom.:

Cov.:

AF XY:

0.000945

AC XY:

AN XY:

33857

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00227

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00171

Gnomad4 OTH

AF:

0.000657

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00121

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00253

AC:

ExAC

AF:

0.00175

AC:

212

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

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

- -

not provided

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hypogonadotropic hypogonadism 1 with or without anosmia

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.2

DANN

Benign

0.099

DEOGEN2

Benign

0.16

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.7

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.15

Vest4

0.19

MVP

0.082

MPC

0.17

ClinPred

0.016

GERP RS

0.46

Varity_R

0.067

gMVP

0.41

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