rs137852517

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_000216.4(ANOS1):c.1187C>T(p.Ser396Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00024 in 1,208,393 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 105 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 13 hem., cov: 23)

Exomes 𝑓: 0.00022 ( 0 hom. 92 hem. )

Consequence

ANOS1
NM_000216.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:2

Conservation

PhyloP100: 4.06

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 was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09063691).

BP6

Variant X-8568252-G-A is Benign according to our data. Variant chrX-8568252-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 10013.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1, Benign=1}.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000404 (45/111386) while in subpopulation AMR AF = 0.00182 (19/10456). AF 95% confidence interval is 0.00119. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position FAILED quality control check.

BS2

High Hemizygotes in GnomAd4 at 13 XL,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANOS1	NM_000216.4 link	c.1187C>T	p.Ser396Leu	missense_variant	Exon 8 of 14	ENST00000262648.8	NP_000207.2	P23352
ANOS1	XM_005274501.5 link	c.1187C>T	p.Ser396Leu	missense_variant	Exon 8 of 9		XP_005274558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANOS1	ENST00000262648.8 link	c.1187C>T	p.Ser396Leu	missense_variant	Exon 8 of 14	1	NM_000216.4	ENSP00000262648.3		P23352
ANOS1	ENST00000488294.1 link	n.277C>T		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.000404

AC:

AN:

111333

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00182

Gnomad ASJ

AF:

0.00415

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000169

Gnomad OTH

AF:

0.00336

GnomAD2 exomes

AF:

0.000292

AC:

AN:

181668

AF XY:

0.000166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000366

Gnomad ASJ exome

AF:

0.00403

Gnomad EAS exome

AF:

0.0000725

Gnomad FIN exome

AF:

0.0000630

Gnomad NFE exome

AF:

0.0000866

Gnomad OTH exome

AF:

0.000445

GnomAD4 exome

AF:

0.000223

AC:

245

AN:

1097007

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

AN XY:

362433

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

26390

Gnomad4 AMR exome

AF:

0.000540

AC:

AN:

35183

Gnomad4 ASJ exome

AF:

0.00506

AC:

AN:

19364

Gnomad4 EAS exome

AF:

0.0000331

AC:

AN:

30186

Gnomad4 SAS exome

AF:

0.0000555

AC:

AN:

54007

Gnomad4 FIN exome

AF:

0.0000494

AC:

AN:

40493

Gnomad4 NFE exome

AF:

0.000111

AC:

AN:

841200

Gnomad4 Remaining exome

AF:

0.000565

AC:

AN:

46050

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<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

AF:

0.000404

AC:

AN:

111386

Hom.:

Cov.:

AF XY:

0.000387

AC XY:

AN XY:

33618

show subpopulations

Gnomad4 AFR

AF:

0.0000326

AC:

0.0000326083

AN:

0.0000326083

Gnomad4 AMR

AF:

0.00182

AC:

0.00181714

AN:

0.00181714

Gnomad4 ASJ

AF:

0.00415

AC:

0.00415094

AN:

0.00415094

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000170

AC:

0.000169504

AN:

0.000169504

Gnomad4 OTH

AF:

0.00331

AC:

0.00331345

AN:

0.00331345

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<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:

0.000353

Hom.:

Bravo

AF:

0.000763

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hypogonadotropic hypogonadism 1 with or without anosmia

Pathogenic:1Benign:1

Oct 20, 2006

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Uncertain:1

May 04, 2022

Mendelics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ANOS1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.091

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.46

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0050

Polyphen

0.62

Vest4

0.096

MVP

0.70

MPC

0.19

ClinPred

0.057

GERP RS

3.0

Varity_R

0.19

gMVP

0.62

Mutation Taster

=91/9

disease causing (ClinVar)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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