rs201866844

chrX-8553929-ATAAG-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000216.4(ANOS1):c.1354+19_1354+22del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 1,187,970 control chromosomes in the GnomAD database, including 411 homozygotes. There are 2,314 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (208 hom., 1137 hem., cov: 21)
  • Exomes 𝑓: 0.0043 (203 hom. 1177 hem.)
• Consequence: ANOS1 NM_000216.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0330

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant X-8553929-ATAAG-A is Benign according to our data. Variant chrX-8553929-ATAAG-A is described in ClinVar as [Benign]. Clinvar id is 516595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANOS1	NM_000216.4	c.1354+19_1354+22del		intron_variant		ENST00000262648.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANOS1	ENST00000262648.8	c.1354+19_1354+22del		intron_variant		1	NM_000216.4	P1

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 4255 AN: 111959 Hom.: 207 Cov.: 21 AF XY: 0.0328 AC XY: 1119 AN XY: 34149

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00889

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000744

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0271

GnomAD3 exomes AF: 0.0106 AC: 1932 AN: 182742 Hom.: 77 AF XY: 0.00688 AC XY: 463 AN XY: 67268

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.00478

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000368

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000368

Gnomad OTH exome AF: 0.00421

GnomAD4 exome AF: 0.00428 AC: 4610 AN: 1075962 Hom.: 203 AF XY: 0.00342 AC XY: 1177 AN XY: 343952

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.00631

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000332

Gnomad4 SAS exome AF: 0.000429

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000190

Gnomad4 OTH exome AF: 0.0107

GnomAD4 genome AF: 0.0382 AC: 4278 AN: 112008 Hom.: 208 Cov.: 21 AF XY: 0.0332 AC XY: 1137 AN XY: 34208

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.00888

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000747

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0268

Alfa AF: 0.0203 Hom.: 111

Bravo AF: 0.0446

Asia WGS AF: 0.0110 AC: 28 AN: 2522

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 13, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hypogonadotropic hypogonadism 1 with or without anosmia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Mar 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs201866844; hg19: chrX-8521970;