chrX-8532889-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000216.4(ANOS1):​c.*106G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000235 in 426,242 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000023 (0 hom. 1 hem.)
• Consequence: ANOS1 NM_000216.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

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

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000235 AC: 1 AN: 426242 Hom.: 0 Cov.: 5 AF XY: 0.00000689 AC XY: 1 AN XY: 145088

African (AFR) AF: 0.0000771 AC: 1 AN: 12972

American (AMR) AF: 0.00 AC: 0 AN: 28168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14242

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 37398

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2927

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 245860

Other (OTH) AF: 0.00 AC: 0 AN: 23448

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.067
DANN	Benign	0.34
PhyloP100		-2.5

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;