Variant X-8532935-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000216.4(ANOS1):c.*60C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 732,249 control chromosomes in the GnomAD database, including 41 homozygotes. There are 2,278 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0084 ( 5 hom., 228 hem., cov: 23)

Exomes 𝑓: 0.011 ( 36 hom. 2050 hem. )

Consequence

ANOS1
NM_000216.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.657

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-8532935-G-A is Benign according to our data. Variant chrX-8532935-G-A is described in ClinVar as [Benign]. Clinvar id is 1291184.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00842 (939/111544) while in subpopulation NFE AF= 0.0129 (686/53164). AF 95% confidence interval is 0.0121. There are 5 homozygotes in gnomad4. There are 228 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 XL,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANOS1	NM_000216.4 link	c.*60C>T		3_prime_UTR_variant	14/14	ENST00000262648.8	NP_000207.2	P23352

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANOS1	ENST00000262648 link	c.*60C>T		3_prime_UTR_variant	14/14	1	NM_000216.4	ENSP00000262648.3		P23352

Frequencies

GnomAD3 genomes

AF:

0.00842

AC:

939

AN:

111491

Hom.:

Cov.:

AF XY:

0.00677

AC XY:

228

AN XY:

33681

show subpopulations

Gnomad AFR

AF:

0.00209

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00930

Gnomad ASJ

AF:

0.0197

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00225

Gnomad FIN

AF:

0.00334

Gnomad MID

AF:

0.00833

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.00799

GnomAD4 exome

AF:

0.0111

AC:

6905

AN:

620705

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

2050

AN XY:

189281

show subpopulations

Gnomad4 AFR exome

AF:

0.00208

Gnomad4 AMR exome

AF:

0.00334

Gnomad4 ASJ exome

AF:

0.0251

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00377

Gnomad4 FIN exome

AF:

0.00316

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.00842

AC:

939

AN:

111544

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

228

AN XY:

33744

show subpopulations

Gnomad4 AFR

AF:

0.00208

Gnomad4 AMR

AF:

0.00929

Gnomad4 ASJ

AF:

0.0197

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00226

Gnomad4 FIN

AF:

0.00334

Gnomad4 NFE

AF:

0.0129

Gnomad4 OTH

AF:

0.00789

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.00867

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.86

CADD

Benign

1.2

DANN

Benign

0.41

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