7-100736982-C-T
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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
NM_003386.3 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: -0.594
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]
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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 |
---|---|---|---|---|---|---|---|---|
ZAN | NM_003386.3 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
ZAN | ENST00000613979.5 | c.427C>T | p.Arg143Cys | missense_variant | 5/48 | 1 | NM_003386.3 | ENSP00000480750 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000254 AC: 36AN: 141622Hom.: 4 Cov.: 26
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GnomAD3 exomes AF: 0.000390 AC: 78AN: 199924Hom.: 12 AF XY: 0.000338 AC XY: 37AN XY: 109332
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GnomAD4 exome AF: 0.000190 AC: 259AN: 1361082Hom.: 45 Cov.: 32 AF XY: 0.000175 AC XY: 118AN XY: 675712
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GnomAD4 genome AF: 0.000254 AC: 36AN: 141622Hom.: 4 Cov.: 26 AF XY: 0.000203 AC XY: 14AN XY: 69080
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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 | Jan 08, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;.;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
.;.;.;D
REVEL
Benign
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;D;.
Vest4
MVP
MPC
0.42
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at