Variant rs314299 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1922C) has been classified as Likely 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

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:

ZAN (HGNC:):

ZAN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 403615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAN	NM_003386.3 linkuse as main transcript	c.5764C>T	p.His1922Tyr	missense_variant	31/48	ENST00000613979.5	NP_003377.2	Q9Y493-1B4DYT6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAN	ENST00000613979.5 linkuse as main transcript	c.5764C>T	p.His1922Tyr	missense_variant	31/48	1	NM_003386.3	ENSP00000480750.1		Q9Y493-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.495

AC:

90251

AN:

182226

Hom.:

19991

AF XY:

0.504

AC XY:

50563

AN XY:

100388

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 SAS exome

AF:

0.447

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000363

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.461

Hom.:

25584

ExAC

AF:

0.469

AC:

45816

Asia WGS

AF:

0.191

AC:

619

AN:

3230

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.026

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.43

.;.;T;T

MetaRNN

Benign

0.0089

T;T;T;T

Sift4G

Uncertain

0.0020

D;D;D;D

Vest4

0.10

ClinPred

0.060

GERP RS

2.6

Varity_R

0.057

gMVP

0.71

Splicing

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