X-8534180-AG-A

Position:

• chrX-8534180-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000216.4(ANOS1):​c.1984+138del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 111,365 control chromosomes in the GnomAD database, including 7 homozygotes. There are 389 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (7 hom., 389 hem., cov: 21)
  • Exomes 𝑓: 0.015 (69 hom. 2343 hem.)
  • Failed GnomAD Quality Control
• Consequence: ANOS1 NM_000216.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.614

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 -10 ACMG points.

• BP6: Variant X-8534180-AG-A is Benign according to our data. Variant chrX-8534180-AG-A is described in ClinVar as [Benign]. Clinvar id is 1238821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0123 (1374/111365) while in subpopulation NFE AF= 0.0187 (991/52978). AF 95% confidence interval is 0.0177. There are 7 homozygotes in gnomad4. There are 389 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 XL,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANOS1	NM_000216.4	c.1984+138del		intron_variant		ENST00000262648.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANOS1	ENST00000262648.8	c.1984+138del		intron_variant		1	NM_000216.4	P1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1374 AN: 111319 Hom.: 7 Cov.: 21 AF XY: 0.0116 AC XY: 389 AN XY: 33473

Gnomad AFR AF: 0.00173

Gnomad AMI AF: 0.0306

Gnomad AMR AF: 0.00352

Gnomad ASJ AF: 0.00454

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00153

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0106

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0153 AC: 7948 AN: 518516 Hom.: 69 AF XY: 0.0151 AC XY: 2343 AN XY: 154850

Gnomad4 AFR exome AF: 0.00171

Gnomad4 AMR exome AF: 0.00260

Gnomad4 ASJ exome AF: 0.00412

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00201

Gnomad4 FIN exome AF: 0.0434

Gnomad4 NFE exome AF: 0.0178

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.0123 AC: 1374 AN: 111365 Hom.: 7 Cov.: 21 AF XY: 0.0116 AC XY: 389 AN XY: 33529

Gnomad4 AFR AF: 0.00172

Gnomad4 AMR AF: 0.00352

Gnomad4 ASJ AF: 0.00454

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00154

Gnomad4 FIN AF: 0.0405

Gnomad4 NFE AF: 0.0187

Gnomad4 OTH AF: 0.0105

Alfa AF: 0.0127 Hom.: 60

Bravo AF: 0.00915

Asia WGS AF: 0.000398 AC: 1 AN: 2520

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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: rs201341529; hg19: chrX-8502221;