X-8536792-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The ENST00000262648.8(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
ENST00000262648.8 missense

Scores

16

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]

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/exons MANE Protein UniProt
ANOS1NM_000216.4 linkuse as main transcriptc.1600G>A p.Val534Ile missense_variant 11/14 ENST00000262648.8 NP_000207.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANOS1ENST00000262648.8 linkuse as main transcriptc.1600G>A p.Val534Ile missense_variant 11/141 NM_000216.4 ENSP00000262648 P1
ANOS1ENST00000481896.1 linkuse as main transcriptn.145G>A non_coding_transcript_exon_variant 1/24

Frequencies

GnomAD3 genomes
AF:
0.546
AC:
60238
AN:
110304
Hom.:
12452
Cov.:
23
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.:
33
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.:
23
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
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsJul 27, 2017- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Hypogonadotropic hypogonadism 1 with or without anosmia Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 19, 2021- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.90
T
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.0030
DANN
Benign
0.18
DEOGEN2
Benign
0.070
T
FATHMM_MKL
Benign
0.0073
N
LIST_S2
Benign
0.47
T
MetaRNN
Benign
0.000031
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.090
N
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.27
T
PROVEAN
Benign
0.23
N
REVEL
Benign
0.074
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.048
MPC
0.085
ClinPred
0.0025
T
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.

Other links and lift over

dbSNP: rs808119; hg19: chrX-8504833; COSMIC: COSV99390489; API