7-100736877-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003386.3(ZAN):​c.322G>A​(p.Asp108Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000202 in 1,486,278 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000049 ( 1 hom., cov: 27)
Exomes 𝑓: 0.000017 ( 5 hom. )

Consequence

ZAN
NM_003386.3 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.03
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.037040025).
BP6
Variant 7-100736877-G-A is Benign according to our data. Variant chr7-100736877-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2360110.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZANNM_003386.3 linkuse as main transcriptc.322G>A p.Asp108Asn missense_variant 5/48 ENST00000613979.5 NP_003377.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZANENST00000613979.5 linkuse as main transcriptc.322G>A p.Asp108Asn missense_variant 5/481 NM_003386.3 ENSP00000480750 P1Q9Y493-1

Frequencies

GnomAD3 genomes
AF:
0.0000494
AC:
7
AN:
141692
Hom.:
1
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.0000513
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000698
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000635
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000281
AC:
5
AN:
177782
Hom.:
0
AF XY:
0.0000310
AC XY:
3
AN XY:
96642
show subpopulations
Gnomad AFR exome
AF:
0.000102
Gnomad AMR exome
AF:
0.0000736
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000717
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000137
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
23
AN:
1344586
Hom.:
5
Cov.:
32
AF XY:
0.0000210
AC XY:
14
AN XY:
666062
show subpopulations
Gnomad4 AFR exome
AF:
0.0000635
Gnomad4 AMR exome
AF:
0.000133
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000125
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000127
Gnomad4 OTH exome
AF:
0.0000358
GnomAD4 genome
AF:
0.0000494
AC:
7
AN:
141692
Hom.:
1
Cov.:
27
AF XY:
0.0000433
AC XY:
3
AN XY:
69220
show subpopulations
Gnomad4 AFR
AF:
0.0000513
Gnomad4 AMR
AF:
0.0000698
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000635
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000130
AC:
1
ExAC
AF:
0.0000266
AC:
3

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 26, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.38
DANN
Benign
0.66
DEOGEN2
Benign
0.0062
T;.;T;.
Eigen
Benign
-2.1
Eigen_PC
Benign
-2.2
FATHMM_MKL
Benign
0.0066
N
LIST_S2
Benign
0.50
.;.;T;T
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.037
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.3
L;L;L;L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.3
.;.;.;N
REVEL
Benign
0.021
Sift4G
Benign
0.82
T;T;T;T
Polyphen
0.0040
B;.;B;.
Vest4
0.16
MVP
0.081
MPC
0.26
ClinPred
0.15
T
GERP RS
-6.0
Varity_R
0.043
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs377492790; hg19: chr7-100334500; API