rs2229013

Variant names:

• chrX-8535755-C-A
• rs2229013
• NM_000216.4:c.1678G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-8535755-C-A
• chrX-8535755-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000216.4(ANOS1):​c.1678G>T​(p.Val560Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V560I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ANOS1 NM_000216.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.732
• Publications: 7 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANOS1	NM_000216.4	c.1678G>T	p.Val560Phe	missense_variant	Exon 12 of 14	ENST00000262648.8	NP_000207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANOS1	ENST00000262648.8	c.1678G>T	p.Val560Phe	missense_variant	Exon 12 of 14	1	NM_000216.4	ENSP00000262648.3
ANOS1	ENST00000481896.1	n.223G>T		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.73
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.23
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.020	D
Polyphen		0.92	P
Vest4		0.41
MutPred		0.62		Loss of stability (P = 0.0849);
MVP		0.18
MPC		0.15
ClinPred		0.70	D
GERP RS		0.37
Varity_R		0.22
gMVP		0.51
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.42		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2229013; hg19: chrX-8503796;