Variant 7-100736522-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003386.3(ZAN):c.146C>T(p.Pro49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,524,020 control chromosomes in the GnomAD database, including 547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 25 hom., cov: 26)

Exomes 𝑓: 0.0027 ( 522 hom. )

Consequence

ZAN
NM_003386.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.41

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006511867).

BP6

Variant 7-100736522-C-T is Benign according to our data. Variant chr7-100736522-C-T is described in ClinVar as [Benign]. Clinvar id is 516855.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00123 (176/142670) while in subpopulation SAS AF= 0.0319 (147/4612). AF 95% confidence interval is 0.0277. There are 25 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZAN	NM_003386.3 linkuse as main transcript	c.146C>T	p.Pro49Leu	missense_variant	4/48	ENST00000613979.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZAN	ENST00000613979.5 linkuse as main transcript	c.146C>T	p.Pro49Leu	missense_variant	4/48	1	NM_003386.3	P1	Q9Y493-1

Frequencies

GnomAD3 genomes

AF:

0.00123

AC:

175

AN:

142572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000139

Gnomad ASJ

AF:

0.00387

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0316

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000142

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00531

AC:

1263

AN:

237938

Hom.:

176

AF XY:

0.00712

AC XY:

919

AN XY:

129122

show subpopulations

Gnomad AFR exome

AF:

0.000334

Gnomad AMR exome

AF:

0.0000300

Gnomad ASJ exome

AF:

0.00341

Gnomad EAS exome

AF:

0.0000567

Gnomad SAS exome

AF:

0.0397

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000225

Gnomad OTH exome

AF:

0.00172

GnomAD4 exome

AF:

0.00265

AC:

3665

AN:

1381350

Hom.:

522

Cov.:

AF XY:

0.00379

AC XY:

2607

AN XY:

687572

show subpopulations

Gnomad4 AFR exome

AF:

0.0000618

Gnomad4 AMR exome

AF:

0.0000463

Gnomad4 ASJ exome

AF:

0.00418

Gnomad4 EAS exome

AF:

0.0000514

Gnomad4 SAS exome

AF:

0.0396

Gnomad4 FIN exome

AF:

0.0000201

Gnomad4 NFE exome

AF:

0.0000373

Gnomad4 OTH exome

AF:

0.00274

GnomAD4 genome

AF:

0.00123

AC:

176

AN:

142670

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

126

AN XY:

69724

show subpopulations

Gnomad4 AFR

AF:

0.000127

Gnomad4 AMR

AF:

0.000139

Gnomad4 ASJ

AF:

0.00387

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0319

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000142

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000546

Hom.:

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.000506

AC:

ExAC

AF:

0.00564

AC:

664

Asia WGS

AF:

0.0160

AC:

AN:

3378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

T;.;T;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.80

.;.;T;T

MetaRNN

Benign

0.0065

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.2

M;M;M;M

MutationTaster

Benign

0.97

D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.3

.;.;.;D

REVEL

Benign

0.26

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.60

MVP

0.46

MPC

0.42

ClinPred

0.057

GERP RS

4.7

Varity_R

0.22

gMVP

0.84

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