X-8533991-AAAG-A

Variant names:

• chrX-8533991-AAAG-A
• rs199520659
• NM_000216.4:c.1984+325_1984+327delCTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000216.4(ANOS1):​c.1984+325_1984+327delCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (16410 hom., 15999 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ANOS1 NM_000216.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 1 with or without anosmia

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant X-8533991-AAAG-A is Benign according to our data. Variant chrX-8533991-AAAG-A is described in ClinVar as Benign. ClinVar VariationId is 1286210.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000216.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANOS1	NM_000216.4	MANE Select	c.1984+325_1984+327delCTT		intron	N/A	NP_000207.2	P23352

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANOS1	ENST00000262648.8	TSL:1 MANE Select	c.1984+325_1984+327delCTT		intron	N/A	ENSP00000262648.3	P23352
	ANOS1	ENST00000921740.1		c.1981+325_1981+327delCTT		intron	N/A	ENSP00000591799.1
	ANOS1	ENST00000921741.1		c.1837+325_1837+327delCTT		intron	N/A	ENSP00000591800.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 65735 AN: 103394 Hom.: 16417 Cov.: 0

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.648

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.635 AC: 65716 AN: 103413 Hom.: 16410 Cov.: 0 AF XY: 0.596 AC XY: 15999 AN XY: 26855

African (AFR) AF: 0.538 AC: 15343 AN: 28526

American (AMR) AF: 0.560 AC: 5301 AN: 9463

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 1774 AN: 2562

East Asian (EAS) AF: 0.661 AC: 2151 AN: 3252

South Asian (SAS) AF: 0.480 AC: 1070 AN: 2227

European-Finnish (FIN) AF: 0.576 AC: 2476 AN: 4298

Middle Eastern (MID) AF: 0.704 AC: 140 AN: 199

European-Non Finnish (NFE) AF: 0.712 AC: 36188 AN: 50848

Other (OTH) AF: 0.647 AC: 904 AN: 1398

Alfa AF: 0.682 Hom.: 4731

Asia WGS AF: 0.571 AC: 1436 AN: 2514

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs199520659; hg19: chrX-8502032;