Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_003386.3(ZAN):c.5764C>T(p.His1922Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

ZAN
NM_003386.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.828

Publications

20 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008918405).

BP6

Variant 7-100773850-C-T is Benign according to our data. Variant chr7-100773850-C-T is described in ClinVar as Benign. ClinVar VariationId is 403615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003386.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZAN	NM_003386.3	MANE Select	c.5764C>T	p.His1922Tyr	missense	Exon 31 of 48	NP_003377.2
ZAN	NM_173059.3		c.5764C>T	p.His1922Tyr	missense	Exon 31 of 46	NP_775082.2
ZAN	NR_111917.2		n.5960C>T		non_coding_transcript_exon	Exon 31 of 48

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZAN	ENST00000613979.5	TSL:1 MANE Select	c.5764C>T	p.His1922Tyr	missense	Exon 31 of 48	ENSP00000480750.1
ZAN	ENST00000620596.4	TSL:1	c.5764C>T	p.His1922Tyr	missense	Exon 31 of 46	ENSP00000481742.1
ZAN	ENST00000538115.5	TSL:1	n.5764C>T		non_coding_transcript_exon	Exon 31 of 47	ENSP00000445091.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.495

AC:

90251

AN:

182226

AF XY:

0.504

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.394

Gnomad ASJ exome

AF:

0.495

Gnomad EAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.543

Gnomad NFE exome

AF:

0.588

Gnomad OTH exome

AF:

0.517

GnomAD4 exome

AF:

0.00000226

AC:

AN:

443222

Hom.:

Cov.:

AF XY:

0.00000454

AC XY:

AN XY:

220396

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

22648

American (AMR)

AF:

0.00

AC:

AN:

25768

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9450

East Asian (EAS)

AF:

0.00

AC:

AN:

37728

South Asian (SAS)

AF:

0.00

AC:

AN:

33888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1190

European-Non Finnish (NFE)

AF:

0.00000363

AC:

AN:

275330

Other (OTH)

AF:

0.00

AC:

AN:

20150

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.451

Hom.:

53107

ExAC

AF:

0.469

AC:

45816

Asia WGS

AF:

0.191

AC:

619

AN:

3230

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.026

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0089

PhyloP100

0.83

Sift4G

Uncertain

0.0020

Vest4

0.10

ClinPred

0.060

GERP RS

2.6

gMVP

0.71

Splicing

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

Publications

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rs314299

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over