rs761235495

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003386.3(ZAN):c.89G>A(p.Arg30His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,506,712 control chromosomes in the GnomAD database, including 4 homozygotes. 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000014 ( 1 hom., cov: 26)

Exomes 𝑓: 0.000016 ( 3 hom. )

Consequence

ZAN
NM_003386.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.92

Variant links:

Genes affected

ZAN (HGNC:12857): (zonadhesin) This gene encodes a protein that functions in the species specificity of sperm adhesion to the egg zona pellucida. The encoded protein is located in the acrosome and may be involved in signaling or gamete recognition. An allelic polymorphism in this gene results in both functional and frameshifted alleles; the reference genome represents the functional allele. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ZAN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026830763).

BP6

Variant 7-100735755-G-A is Benign according to our data. Variant chr7-100735755-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3191755.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZAN	NM_003386.3 link	c.89G>A	p.Arg30His	missense_variant	Exon 3 of 48	ENST00000613979.5	NP_003377.2	Q9Y493-1B4DYT6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZAN	ENST00000613979.5 link	c.89G>A	p.Arg30His	missense_variant	Exon 3 of 48	1	NM_003386.3	ENSP00000480750.1		Q9Y493-1

Frequencies

GnomAD3 genomes

AF:

0.0000143

AC:

AN:

139706

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000406

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000364

AC:

AN:

219922

AF XY:

0.0000168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.0000161

AC:

AN:

1367006

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

679530

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32098

American (AMR)

AF:

0.0000244

AC:

AN:

41056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24798

East Asian (EAS)

AF:

0.000259

AC:

AN:

38538

South Asian (SAS)

AF:

0.00

AC:

AN:

82842

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

0.00000965

AC:

AN:

1036518

Other (OTH)

AF:

0.0000176

AC:

AN:

56680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000143

AC:

AN:

139706

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

67984

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38188

American (AMR)

AF:

0.00

AC:

AN:

14040

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3316

East Asian (EAS)

AF:

0.000406

AC:

AN:

4922

South Asian (SAS)

AF:

0.00

AC:

AN:

4504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62538

Other (OTH)

AF:

0.00

AC:

AN:

1908

Alfa

AF:

0.0000488

Hom.:

ExAC

AF:

0.0000260

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 09, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.040

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

T;.;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.54

.;.;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.027

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;N;N;N

PhyloP100

-2.9

PrimateAI

Benign

0.22

PROVEAN

Benign

0.11

.;.;.;N

REVEL

Benign

0.018

Sift4G

Benign

0.62

T;T;T;T

Polyphen

0.0010

B;.;B;.

Vest4

0.025

MutPred

0.36

Gain of ubiquitination at K26 (P = 0.0343);Gain of ubiquitination at K26 (P = 0.0343);Gain of ubiquitination at K26 (P = 0.0343);Gain of ubiquitination at K26 (P = 0.0343);

MVP

0.030

MPC

0.096

ClinPred

0.046

GERP RS

-9.0

Varity_R

0.028

gMVP

0.47

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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.

rs761235495

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over