9-128731384-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006336.4(ZER1):​c.2254G>A​(p.Glu752Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000745 in 134,212 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000075 ( 0 hom., cov: 30)

Consequence

ZER1
NM_006336.4 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.66
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]
ZDHHC12-DT (HGNC:55873): (ZDHHC12 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZER1NM_006336.4 linkc.2254G>A p.Glu752Lys missense_variant Exon 16 of 16 ENST00000291900.7 NP_006327.2 Q7Z7L7A0A024R8B0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZER1ENST00000291900.7 linkc.2254G>A p.Glu752Lys missense_variant Exon 16 of 16 1 NM_006336.4 ENSP00000291900.2 Q7Z7L7
ZDHHC12-DTENST00000443631.2 linkn.202-1458C>T intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.00000745
AC:
1
AN:
134212
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000157
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000745
AC:
1
AN:
134212
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
64104
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000157
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2254G>A (p.E752K) alteration is located in exon 16 (coding exon 15) of the ZER1 gene. This alteration results from a G to A substitution at nucleotide position 2254, causing the glutamic acid (E) at amino acid position 752 to be replaced by a lysine (K). 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
0.13
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.074
T
Eigen
Uncertain
0.65
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.048
D
MetaRNN
Uncertain
0.43
T
MetaSVM
Benign
-0.55
T
MutationAssessor
Benign
1.3
L
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.6
N
REVEL
Uncertain
0.35
Sift
Benign
0.090
T
Sift4G
Benign
0.21
T
Polyphen
0.99
D
Vest4
0.50
MutPred
0.40
Gain of MoRF binding (P = 0.0019);
MVP
0.14
MPC
0.59
ClinPred
0.92
D
GERP RS
5.7
Varity_R
0.37
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs1457212628; hg19: chr9-131493663; API