X-8536852-C-T

Position:

• chrX-8536852-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_000216.4(ANOS1):​c.1540G>A​(p.Glu514Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ANOS1 NM_000216.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.96

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.901
• PP5: Variant X-8536852-C-T is Pathogenic according to our data. Variant chrX-8536852-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 10008.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANOS1	NM_000216.4	c.1540G>A	p.Glu514Lys	missense_variant	11/14	ENST00000262648.8	NP_000207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANOS1	ENST00000262648.8	c.1540G>A	p.Glu514Lys	missense_variant	11/14	1	NM_000216.4	ENSP00000262648.3
ANOS1	ENST00000481896.1	n.85G>A		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypogonadotropic hypogonadism 1 with or without anosmia Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.021	D
Sift4G	Benign	0.080	T
Polyphen		0.99	D
Vest4		0.37
MutPred		0.82		Gain of MoRF binding (P = 0.0252);
MVP		0.76
MPC		0.27
ClinPred		0.63	D
GERP RS		4.0
Varity_R		0.44
gMVP		0.68

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: rs137852515; hg19: chrX-8504893;