chrX-8532889-C-T

Variant names:

• chrX-8532889-C-T
• rs139805162
• NM_000216.4:c.*106G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000216.4(ANOS1):​c.*106G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 537,814 control chromosomes in the GnomAD database, including 13 homozygotes. There are 327 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (11 hom., 210 hem., cov: 23)
  • Exomes 𝑓: 0.0011 (2 hom. 117 hem.)
• Consequence: ANOS1 NM_000216.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.48
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant X-8532889-C-T is Benign according to our data. Variant chrX-8532889-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1342039.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00684 (763/111575) while in subpopulation AFR AF = 0.0233 (716/30687). AF 95% confidence interval is 0.0219. There are 11 homozygotes in GnomAd4. There are 210 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High AC in GnomAd4 at 763 XL,AD gene.

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.*106G>A		3_prime_UTR	Exon 14 of 14	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.*106G>A		3_prime_UTR	Exon 14 of 14	ENSP00000262648.3	P23352
	ANOS1	ENST00000921740.1		c.*106G>A		3_prime_UTR	Exon 14 of 14	ENSP00000591799.1
	ANOS1	ENST00000921741.1		c.*106G>A		3_prime_UTR	Exon 13 of 13	ENSP00000591800.1

Frequencies

GnomAD3 genomes AF: 0.00682 AC: 761 AN: 111523 Hom.: 11 Cov.: 23

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00306

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000564

Gnomad OTH AF: 0.00799

GnomAD4 exome AF: 0.00108 AC: 461 AN: 426239 Hom.: 2 Cov.: 5 AF XY: 0.000806 AC XY: 117 AN XY: 145087

African (AFR) AF: 0.0248 AC: 322 AN: 12972

American (AMR) AF: 0.00163 AC: 46 AN: 28168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14241

East Asian (EAS) AF: 0.00 AC: 0 AN: 24474

South Asian (SAS) AF: 0.0000535 AC: 2 AN: 37398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36753

Middle Eastern (MID) AF: 0.000342 AC: 1 AN: 2927

European-Non Finnish (NFE) AF: 0.0000935 AC: 23 AN: 245858

Other (OTH) AF: 0.00286 AC: 67 AN: 23448

GnomAD4 genome AF: 0.00684 AC: 763 AN: 111575 Hom.: 11 Cov.: 23 AF XY: 0.00622 AC XY: 210 AN XY: 33767

African (AFR) AF: 0.0233 AC: 716 AN: 30687

American (AMR) AF: 0.00305 AC: 32 AN: 10482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3534

South Asian (SAS) AF: 0.00 AC: 0 AN: 2638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6013

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000564 AC: 3 AN: 53154

Other (OTH) AF: 0.00789 AC: 12 AN: 1520

Alfa AF: 0.00517 Hom.: 21

Bravo AF: 0.00788

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.080
DANN	Benign	0.57
PhyloP100		-2.5
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

Other links and lift over

dbSNP: rs139805162; hg19: chrX-8500930;