Genetic Variant NM_003386.3:c.5649G>A (chr7-100773735-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003386.3(ZAN):c.5649G>A(p.Trp1883*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0428 in 1,609,900 control chromosomes in the GnomAD database, including 11,702 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.057 ( 1284 hom., cov: 33)

Exomes 𝑓: 0.041 ( 10418 hom. )

Consequence

ZAN
NM_003386.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.90

Publications

22 publications found

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZAN	NM_003386.3 link	c.5649G>A	p.Trp1883*	stop_gained	Exon 31 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.5649G>A	p.Trp1883*	stop_gained	Exon 31 of 48	1	NM_003386.3	ENSP00000480750.1		Q9Y493-1

Frequencies

GnomAD3 genomes

AF:

0.0568

AC:

8640

AN:

152088

Hom.:

1276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.0388

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00529

Gnomad OTH

AF:

0.0636

GnomAD2 exomes

AF:

0.114

AC:

27608

AN:

241580

AF XY:

0.103

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.346

Gnomad ASJ exome

AF:

0.0455

Gnomad EAS exome

AF:

0.530

Gnomad FIN exome

AF:

0.0390

Gnomad NFE exome

AF:

0.00622

Gnomad OTH exome

AF:

0.0732

GnomAD4 exome

AF:

0.0413

AC:

60195

AN:

1457690

Hom.:

10418

Cov.:

AF XY:

0.0424

AC XY:

30759

AN XY:

724778

show subpopulations

African (AFR)

AF:

0.0191

AC:

639

AN:

33372

American (AMR)

AF:

0.332

AC:

14586

AN:

43986

Ashkenazi Jewish (ASJ)

AF:

0.0446

AC:

1158

AN:

25988

East Asian (EAS)

AF:

0.566

AC:

22367

AN:

39540

South Asian (SAS)

AF:

0.128

AC:

10970

AN:

85430

European-Finnish (FIN)

AF:

0.0359

AC:

1908

AN:

53096

Middle Eastern (MID)

AF:

0.0201

AC:

116

AN:

5764

European-Non Finnish (NFE)

AF:

0.00439

AC:

4874

AN:

1110246

Other (OTH)

AF:

0.0594

AC:

3577

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

2498

4996

7495

9993

12491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.0569

AC:

8665

AN:

152210

Hom.:

1284

Cov.:

AF XY:

0.0659

AC XY:

4902

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0219

AC:

910

AN:

41562

American (AMR)

AF:

0.218

AC:

3332

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.0415

AC:

144

AN:

3466

East Asian (EAS)

AF:

0.512

AC:

2640

AN:

5154

South Asian (SAS)

AF:

0.148

AC:

716

AN:

4822

European-Finnish (FIN)

AF:

0.0388

AC:

412

AN:

10618

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00529

AC:

360

AN:

68012

Other (OTH)

AF:

0.0686

AC:

145

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

313

626

939

1252

1565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0345

Hom.:

3877

Bravo

AF:

0.0695

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.0236

AC:

ESP6500EA

AF:

0.00711

AC:

ExAC

AF:

0.100

AC:

12110

Asia WGS

AF:

0.283

AC:

983

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.63

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.91

PhyloP100

4.9

Vest4

0.79

GERP RS

4.4

Mutation Taster

=34/166

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over