rs10521595

Variant names:

• chrX-8636435-T-C
• rs10521595
• NM_000216.4:c.256-12765A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000216.4(ANOS1):​c.256-12765A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 111,819 control chromosomes in the GnomAD database, including 779 homozygotes. There are 3,615 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (779 hom., 3615 hem., cov: 23)
• Consequence: ANOS1 NM_000216.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• 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: ClinGen, Labcorp Genetics (formerly Invitae)
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANOS1	NM_000216.4	c.256-12765A>G		intron_variant	Intron 2 of 13	ENST00000262648.8	NP_000207.2
ANOS1	NM_001440775.1	c.256-12765A>G		intron_variant	Intron 2 of 8		NP_001427704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANOS1	ENST00000262648.8	c.256-12765A>G		intron_variant	Intron 2 of 13	1	NM_000216.4	ENSP00000262648.3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 11734 AN: 111767 Hom.: 779 Cov.: 23

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0130

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.0310

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0992

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

GnomAD4 genome AF: 0.105 AC: 11741 AN: 111819 Hom.: 779 Cov.: 23 AF XY: 0.106 AC XY: 3615 AN XY: 34033

African (AFR) AF: 0.220 AC: 6751 AN: 30700

American (AMR) AF: 0.173 AC: 1816 AN: 10497

Ashkenazi Jewish (ASJ) AF: 0.0310 AC: 82 AN: 2648

East Asian (EAS) AF: 0.118 AC: 418 AN: 3533

South Asian (SAS) AF: 0.250 AC: 670 AN: 2681

European-Finnish (FIN) AF: 0.0690 AC: 420 AN: 6086

Middle Eastern (MID) AF: 0.0231 AC: 5 AN: 216

European-Non Finnish (NFE) AF: 0.0267 AC: 1420 AN: 53237

Other (OTH) AF: 0.0980 AC: 150 AN: 1531

Alfa AF: 0.0674 Hom.: 981

Bravo AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.56
PhyloP100		-0.33
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: rs10521595; hg19: chrX-8604476;