Variant X-8597153-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP5_Moderate

The NM_000216.4(ANOS1):c.422G>A(p.Ser141Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,210,028 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

ANOS1
NM_000216.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.85

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 Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a domain WAP (size 49) in uniprot entity KALM_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_000216.4

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant X-8597153-C-T is Pathogenic according to our data. Variant chrX-8597153-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 431157.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANOS1	NM_000216.4 linkuse as main transcript	c.422G>A	p.Ser141Asn	missense_variant	4/14	ENST00000262648.8	NP_000207.2	P23352
ANOS1	XM_005274501.5 linkuse as main transcript	c.422G>A	p.Ser141Asn	missense_variant	4/9		XP_005274558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANOS1	ENST00000262648.8 linkuse as main transcript	c.422G>A	p.Ser141Asn	missense_variant	4/14	1	NM_000216.4	ENSP00000262648.3		P23352

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111866

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34036

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1098162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363526

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111866

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34036

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hypogonadotropic hypogonadism 1 with or without anosmia

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris

Jan 06, 2017

hypogonadism -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.95

MetaRNN

Uncertain

0.72

MetaSVM

Uncertain

-0.079

MutationAssessor

Benign

1.9

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.35

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.40

MutPred

0.64

Loss of glycosylation at S141 (P = 0.0013);

MVP

0.84

MPC

1.9

ClinPred

0.94

GERP RS

4.5

Varity_R

0.61

gMVP

0.78

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