7-100736982-C-T

Variant summary

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

The NM_003386.3(ZAN):​c.427C>T​(p.Arg143Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,502,704 control chromosomes in the GnomAD database, including 49 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: 0.00019 ( 45 hom. )

Consequence

ZAN
NM_003386.3 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.594
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 -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.009850055).
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZANNM_003386.3 linkuse as main transcriptc.427C>T p.Arg143Cys 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.427C>T p.Arg143Cys missense_variant 5/481 NM_003386.3 ENSP00000480750 P1Q9Y493-1

Frequencies

GnomAD3 genomes
AF:
0.000254
AC:
36
AN:
141622
Hom.:
4
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.000155
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000209
Gnomad ASJ
AF:
0.00447
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000190
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000390
AC:
78
AN:
199924
Hom.:
12
AF XY:
0.000338
AC XY:
37
AN XY:
109332
show subpopulations
Gnomad AFR exome
AF:
0.0000910
Gnomad AMR exome
AF:
0.000402
Gnomad ASJ exome
AF:
0.00473
Gnomad EAS exome
AF:
0.000126
Gnomad SAS exome
AF:
0.0000373
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000198
Gnomad OTH exome
AF:
0.000590
GnomAD4 exome
AF:
0.000190
AC:
259
AN:
1361082
Hom.:
45
Cov.:
32
AF XY:
0.000175
AC XY:
118
AN XY:
675712
show subpopulations
Gnomad4 AFR exome
AF:
0.0000626
Gnomad4 AMR exome
AF:
0.000397
Gnomad4 ASJ exome
AF:
0.00393
Gnomad4 EAS exome
AF:
0.0000785
Gnomad4 SAS exome
AF:
0.0000245
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000986
Gnomad4 OTH exome
AF:
0.000584
GnomAD4 genome
AF:
0.000254
AC:
36
AN:
141622
Hom.:
4
Cov.:
26
AF XY:
0.000203
AC XY:
14
AN XY:
69080
show subpopulations
Gnomad4 AFR
AF:
0.000155
Gnomad4 AMR
AF:
0.000209
Gnomad4 ASJ
AF:
0.00447
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000190
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00146
Hom.:
7
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000258
AC:
2
ExAC
AF:
0.000289
AC:
33

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 submitterclinical testingAmbry GeneticsJan 08, 2024The c.427C>T (p.R143C) 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 427, causing the arginine (R) at amino acid position 143 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
0.18
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.017
T;.;T;.
Eigen
Benign
-0.80
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.48
.;.;T;T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.0099
T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.7
L;L;L;L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-2.6
.;.;.;D
REVEL
Benign
0.13
Sift4G
Uncertain
0.012
D;D;D;D
Polyphen
0.96
D;.;D;.
Vest4
0.22
MVP
0.29
MPC
0.42
ClinPred
0.63
D
GERP RS
-2.4
Varity_R
0.099
gMVP
0.80

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.

Other links and lift over

dbSNP: rs200501007; hg19: chr7-100334605; COSMIC: COSV61814354; API