NM_000216.4:c.1532C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000216.4(ANOS1):c.1532C>A(p.Ser511Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,205,846 control chromosomes in the GnomAD database, including 4 homozygotes. There are 713 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., 32 hem., cov: 22)

Exomes 𝑓: 0.0017 ( 4 hom. 681 hem. )

Consequence

ANOS1
NM_000216.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:5

Conservation

PhyloP100: 2.50

Publications

7 publications found

Variant links:

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

ANOS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012378961).

BP6

Variant X-8536860-G-T is Benign according to our data. Variant chrX-8536860-G-T is described in ClinVar as Benign. ClinVar VariationId is 463525.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00106 (118/111661) while in subpopulation SAS AF = 0.00227 (6/2644). AF 95% confidence interval is 0.00143. There are 0 homozygotes in GnomAd4. There are 32 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High AC in GnomAd4 at 118 XL,AD gene.

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.1532C>A	p.Ser511Tyr	missense	Exon 11 of 14	NP_000207.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ANOS1	ENST00000262648.8	TSL:1 MANE Select	c.1532C>A	p.Ser511Tyr	missense	Exon 11 of 14	ENSP00000262648.3
ANOS1	ENST00000921740.1		c.1529C>A	p.Ser510Tyr	missense	Exon 11 of 14	ENSP00000591799.1
ANOS1	ENST00000921741.1		c.1385C>A	p.Ser462Tyr	missense	Exon 10 of 13	ENSP00000591800.1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

118

AN:

111609

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00226

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00171

Gnomad OTH

AF:

0.000666

GnomAD2 exomes

AF:

0.00149

AC:

271

AN:

181586

AF XY:

0.00200

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.000512

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000628

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00173

AC:

1892

AN:

1094185

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

681

AN XY:

359629

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26337

American (AMR)

AF:

0.000682

AC:

AN:

35177

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19358

East Asian (EAS)

AF:

0.00

AC:

AN:

30181

South Asian (SAS)

AF:

0.00273

AC:

147

AN:

53931

European-Finnish (FIN)

AF:

0.000123

AC:

AN:

40513

Middle Eastern (MID)

AF:

0.00702

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00192

AC:

1613

AN:

838589

Other (OTH)

AF:

0.00152

AC:

AN:

45968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

129

194

258

323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00106

AC:

118

AN:

111661

Hom.:

Cov.:

AF XY:

0.000945

AC XY:

AN XY:

33857

show subpopulations

African (AFR)

AF:

0.000195

AC:

AN:

30756

American (AMR)

AF:

0.00105

AC:

AN:

10486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3531

South Asian (SAS)

AF:

0.00227

AC:

AN:

2644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6026

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00171

AC:

AN:

53153

Other (OTH)

AF:

0.000657

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.00121

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00253

AC:

ExAC

AF:

0.00175

AC:

212

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Hypogonadotropic hypogonadism 1 with or without anosmia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.2

(source)

DANN

Benign

0.099

DEOGEN2

Benign

0.16

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

PhyloP100

2.5

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.7

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.15

Vest4

0.19

MVP

0.082

MPC

0.17

ClinPred

0.016

GERP RS

0.46

Varity_R

0.067

gMVP

0.41

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over