X-8532889-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 XL,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANOS1	NM_000216.4	c.*106G>A		3_prime_UTR_variant	14/14	ENST00000262648.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANOS1	ENST00000262648.8	c.*106G>A		3_prime_UTR_variant	14/14	1	NM_000216.4	P1

Frequencies

GnomAD3 genomes AF: 0.00682 AC: 761 AN: 111523 Hom.: 11 Cov.: 23 AF XY: 0.00620 AC XY: 209 AN XY: 33705

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

Gnomad4 AFR exome AF: 0.0248

Gnomad4 AMR exome AF: 0.00163

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000535

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000935

Gnomad4 OTH exome AF: 0.00286

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

Gnomad4 AFR AF: 0.0233

Gnomad4 AMR AF: 0.00305

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000564

Gnomad4 OTH AF: 0.00789

Alfa AF: 0.00564 Hom.: 21

Bravo AF: 0.00788

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.080
Dann	Benign	0.57

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: rs139805162; hg19: chrX-8500930;