Genetic Variant ZAN:p.Arg98Pro (chr7-100736848-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003386.3(ZAN):c.293G>C(p.Arg98Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000746 in 1,340,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R98H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

ZAN
NM_003386.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.12

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12665784).

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	UniProt
ZAN	NM_003386.3	MANE Select	c.293G>C	p.Arg98Pro	missense	Exon 5 of 48	NP_003377.2	Q9Y493-1
ZAN	NM_173059.3		c.293G>C	p.Arg98Pro	missense	Exon 5 of 46	NP_775082.2	Q9Y493-6
ZAN	NR_111917.2		n.489G>C		non_coding_transcript_exon	Exon 5 of 48

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZAN	ENST00000613979.5	TSL:1 MANE Select	c.293G>C	p.Arg98Pro	missense	Exon 5 of 48	ENSP00000480750.1	Q9Y493-1
ZAN	ENST00000620596.4	TSL:1	c.293G>C	p.Arg98Pro	missense	Exon 5 of 46	ENSP00000481742.1	Q9Y493-6
ZAN	ENST00000538115.5	TSL:1	n.293G>C		non_coding_transcript_exon	Exon 5 of 47	ENSP00000445091.2	Q9Y493-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.46e-7

AC:

AN:

1340226

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

663706

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31418

American (AMR)

AF:

0.00

AC:

AN:

37078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24434

East Asian (EAS)

AF:

0.00

AC:

AN:

36854

South Asian (SAS)

AF:

0.00

AC:

AN:

79822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45270

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1023998

Other (OTH)

AF:

0.00

AC:

AN:

55738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.0020

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.0099

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.38

M_CAP

Benign

0.0048

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

PhyloP100

-4.1

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.27

Sift4G

Benign

0.20

Polyphen

0.0060

Vest4

0.17

MutPred

0.61

Loss of solvent accessibility (P = 0.0013)

MVP

0.061

MPC

0.17

ClinPred

0.52

GERP RS

-8.8

Varity_R

0.14

gMVP

0.92

Mutation Taster

=89/11

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over