9-128741566-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006336.4(ZER1):​c.1706A>G​(p.Asn569Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZER1
NM_006336.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23
Variant links:
Genes affected
ZER1 (HGNC:30960): (zyg-11 related cell cycle regulator) This gene encodes a subunit of an E3 ubiquitin ligase complex that may be involved in meiosis. The encoded protein contains three leucine-rich repeat motifs. [provided by RefSeq, Nov 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0971109).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZER1NM_006336.4 linkc.1706A>G p.Asn569Ser missense_variant Exon 11 of 16 ENST00000291900.7 NP_006327.2 Q7Z7L7A0A024R8B0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZER1ENST00000291900.7 linkc.1706A>G p.Asn569Ser missense_variant Exon 11 of 16 1 NM_006336.4 ENSP00000291900.2 Q7Z7L7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1706A>G (p.N569S) alteration is located in exon 11 (coding exon 10) of the ZER1 gene. This alteration results from a A to G substitution at nucleotide position 1706, causing the asparagine (N) at amino acid position 569 to be replaced by a serine (S). 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
0.055
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
15
DANN
Benign
0.91
DEOGEN2
Benign
0.079
T
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.86
D
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.097
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.14
N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.032
Sift
Benign
0.27
T
Sift4G
Benign
0.65
T
Polyphen
0.0
B
Vest4
0.090
MutPred
0.40
Loss of catalytic residue at N569 (P = 0.0317);
MVP
0.068
MPC
0.85
ClinPred
0.10
T
GERP RS
1.5
Varity_R
0.044
gMVP
0.016

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs1564395378; hg19: chr9-131503845; API