Variant 7-100736985-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000613979.5(ZAN):c.430C>T(p.Arg144Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000412 in 1,502,618 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 4 hom., cov: 26)

Exomes 𝑓: 0.00043 ( 102 hom. )

Consequence

ZAN
ENST00000613979.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03756377).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAN	NM_003386.3 linkuse as main transcript	c.430C>T	p.Arg144Cys	missense_variant	5/48	ENST00000613979.5	NP_003377.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAN	ENST00000613979.5 linkuse as main transcript	c.430C>T	p.Arg144Cys	missense_variant	5/48	1	NM_003386.3	ENSP00000480750	P1	Q9Y493-1

Frequencies

GnomAD3 genomes

AF:

0.000254

AC:

AN:

141688

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000515

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000696

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00101

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000428

Gnomad OTH

AF:

0.000520

GnomAD3 exomes

AF:

0.000535

AC:

107

AN:

199974

Hom.:

AF XY:

0.000448

AC XY:

AN XY:

109318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000101

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00183

Gnomad SAS exome

AF:

0.0000373

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000665

Gnomad OTH exome

AF:

0.000393

GnomAD4 exome

AF:

0.000428

AC:

583

AN:

1360930

Hom.:

102

Cov.:

AF XY:

0.000413

AC XY:

279

AN XY:

675556

show subpopulations

Gnomad4 AFR exome

AF:

0.0000313

Gnomad4 AMR exome

AF:

0.0000745

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.00128

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000450

Gnomad4 OTH exome

AF:

0.000549

GnomAD4 genome

AF:

0.000254

AC:

AN:

141688

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

AN XY:

69140

show subpopulations

Gnomad4 AFR

AF:

0.0000515

Gnomad4 AMR

AF:

0.0000696

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00101

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000428

Gnomad4 OTH

AF:

0.000520

Alfa

AF:

0.000634

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000129

AC:

ExAC

AF:

0.000491

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2022

The c.430C>T (p.R144C) alteration is located in exon 5 (coding exon 4) of the ZAN gene. This alteration results from a C to T substitution at nucleotide position 430, causing the arginine (R) at amino acid position 144 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

T;.;T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.65

.;.;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.038

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

M;M;M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.0

.;.;.;D

REVEL

Benign

0.13

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.40

MVP

0.33

MPC

0.46

ClinPred

0.088

GERP RS

3.3

Varity_R

0.14

gMVP

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over