chrX-8533079-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000216.4(ANOS1):​c.1985-26G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 953,021 control chromosomes in the GnomAD database, including 29,369 homozygotes. There are 83,369 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.30 ( 3873 hom., 9871 hem., cov: 23)
Exomes 𝑓: 0.29 ( 25496 hom. 73498 hem. )

Consequence

ANOS1
NM_000216.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.186
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 -20 ACMG points.

BP4
This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant X-8533079-C-A is Benign according to our data. Variant chrX-8533079-C-A is described in ClinVar as [Benign]. Clinvar id is 1236328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANOS1NM_000216.4 linkuse as main transcriptc.1985-26G>T intron_variant ENST00000262648.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANOS1ENST00000262648.8 linkuse as main transcriptc.1985-26G>T intron_variant 1 NM_000216.4 P1

Frequencies

GnomAD3 genomes
AF:
0.304
AC:
33808
AN:
111112
Hom.:
3873
Cov.:
23
AF XY:
0.296
AC XY:
9854
AN XY:
33344
show subpopulations
Gnomad AFR
AF:
0.327
Gnomad AMI
AF:
0.326
Gnomad AMR
AF:
0.207
Gnomad ASJ
AF:
0.334
Gnomad EAS
AF:
0.574
Gnomad SAS
AF:
0.289
Gnomad FIN
AF:
0.310
Gnomad MID
AF:
0.289
Gnomad NFE
AF:
0.292
Gnomad OTH
AF:
0.303
GnomAD3 exomes
AF:
0.298
AC:
51473
AN:
172643
Hom.:
5638
AF XY:
0.303
AC XY:
17655
AN XY:
58267
show subpopulations
Gnomad AFR exome
AF:
0.338
Gnomad AMR exome
AF:
0.134
Gnomad ASJ exome
AF:
0.339
Gnomad EAS exome
AF:
0.579
Gnomad SAS exome
AF:
0.315
Gnomad FIN exome
AF:
0.313
Gnomad NFE exome
AF:
0.290
Gnomad OTH exome
AF:
0.290
GnomAD4 exome
AF:
0.289
AC:
243402
AN:
841857
Hom.:
25496
Cov.:
15
AF XY:
0.313
AC XY:
73498
AN XY:
234725
show subpopulations
Gnomad4 AFR exome
AF:
0.331
Gnomad4 AMR exome
AF:
0.149
Gnomad4 ASJ exome
AF:
0.335
Gnomad4 EAS exome
AF:
0.550
Gnomad4 SAS exome
AF:
0.318
Gnomad4 FIN exome
AF:
0.302
Gnomad4 NFE exome
AF:
0.278
Gnomad4 OTH exome
AF:
0.305
GnomAD4 genome
AF:
0.304
AC:
33824
AN:
111164
Hom.:
3873
Cov.:
23
AF XY:
0.295
AC XY:
9871
AN XY:
33406
show subpopulations
Gnomad4 AFR
AF:
0.327
Gnomad4 AMR
AF:
0.207
Gnomad4 ASJ
AF:
0.334
Gnomad4 EAS
AF:
0.573
Gnomad4 SAS
AF:
0.289
Gnomad4 FIN
AF:
0.310
Gnomad4 NFE
AF:
0.292
Gnomad4 OTH
AF:
0.306
Alfa
AF:
0.319
Hom.:
3042
Bravo
AF:
0.301

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.70
DANN
Benign
0.44
BranchPoint Hunter
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs41303179; hg19: chrX-8501120; COSMIC: COSV52924123; COSMIC: COSV52924123; API