Variant X-8535600-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_000216.4(ANOS1):c.1833C>T(p.Ile611=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 12116 hom., 17436 hem., cov: 23)

Exomes 𝑓: 0.62 ( 147868 hom. 220049 hem. )

Failed GnomAD Quality Control

Consequence

ANOS1
NM_000216.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.356

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant X-8535600-G-A is Benign according to our data. Variant chrX-8535600-G-A is described in ClinVar as [Benign]. Clinvar id is 255564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-8535600-G-A is described in Lovd as [Benign]. Variant chrX-8535600-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.356 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANOS1	NM_000216.4 linkuse as main transcript	c.1833C>T	p.Ile611=	synonymous_variant	12/14	ENST00000262648.8	NP_000207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANOS1	ENST00000262648.8 linkuse as main transcript	c.1833C>T	p.Ile611=	synonymous_variant	12/14	1	NM_000216.4	ENSP00000262648	P1
ANOS1	ENST00000481896.1 linkuse as main transcript	n.378C>T		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

59407

AN:

110963

Hom.:

12123

Cov.:

AF XY:

0.525

AC XY:

17430

AN XY:

33225

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.610

Gnomad NFE

AF:

0.655

Gnomad OTH

AF:

0.555

GnomAD3 exomes

AF:

0.555

AC:

100457

AN:

180887

Hom.:

18903

AF XY:

0.559

AC XY:

36673

AN XY:

65621

show subpopulations

Gnomad AFR exome

AF:

0.333

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.657

Gnomad EAS exome

AF:

0.655

Gnomad SAS exome

AF:

0.403

Gnomad FIN exome

AF:

0.594

Gnomad NFE exome

AF:

0.658

Gnomad OTH exome

AF:

0.594

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.624

AC:

680341

AN:

1090675

Hom.:

147868

Cov.:

AF XY:

0.616

AC XY:

220049

AN XY:

357275

show subpopulations

Gnomad4 AFR exome

AF:

0.323

Gnomad4 AMR exome

AF:

0.371

Gnomad4 ASJ exome

AF:

0.652

Gnomad4 EAS exome

AF:

0.665

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.588

Gnomad4 NFE exome

AF:

0.659

Gnomad4 OTH exome

AF:

0.607

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.535

AC:

59394

AN:

111017

Hom.:

12116

Cov.:

AF XY:

0.524

AC XY:

17436

AN XY:

33289

show subpopulations

Gnomad4 AFR

AF:

0.331

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.630

Gnomad4 EAS

AF:

0.653

Gnomad4 SAS

AF:

0.377

Gnomad4 FIN

AF:

0.585

Gnomad4 NFE

AF:

0.654

Gnomad4 OTH

AF:

0.558

Alfa

AF:

0.532

Hom.:

12167

Bravo

AF:

0.523

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 27, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Hypogonadotropic hypogonadism 1 with or without anosmia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.20

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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