7-100404189-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001386010.1(ZCWPW1):​c.1310G>A​(p.Gly437Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZCWPW1
NM_001386010.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.371
Variant links:
Genes affected
ZCWPW1 (HGNC:23486): (zinc finger CW-type and PWWP domain containing 1) Enables methyl-CpG binding activity and methylated histone binding activity. Predicted to be involved in meiosis I; positive regulation of DNA metabolic process; and spermatogenesis. Predicted to act upstream of or within homologous chromosome pairing at meiosis. Predicted to be located in XY body. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028608471).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZCWPW1NM_001386010.1 linkc.1310G>A p.Gly437Glu missense_variant Exon 14 of 18 ENST00000684423.1 NP_001372939.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZCWPW1ENST00000684423.1 linkc.1310G>A p.Gly437Glu missense_variant Exon 14 of 18 NM_001386010.1 ENSP00000507762.1 A0A804HK41
ENSG00000289690ENST00000695708.1 linkc.-1208+4577C>T intron_variant Intron 3 of 9 ENSP00000512108.1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152182
Hom.:
0
Cov.:
31
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:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000240
AC:
6
AN:
249502
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135370
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000278
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461802
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152182
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000248
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 31, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1307G>A (p.G436E) alteration is located in exon 14 (coding exon 12) of the ZCWPW1 gene. This alteration results from a G to A substitution at nucleotide position 1307, causing the glycine (G) at amino acid position 436 to be replaced by a glutamic acid (E). 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
0.086
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
9.0
DANN
Benign
0.94
DEOGEN2
Benign
0.0019
T;.;.;.
Eigen
Benign
-0.94
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.66
T;T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.029
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;.;.;.
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.040
N;N;N;N
REVEL
Benign
0.036
Sift
Benign
0.35
T;T;T;T
Sift4G
Benign
0.24
T;T;T;T
Polyphen
0.058
B;B;.;.
Vest4
0.10
MutPred
0.24
Gain of solvent accessibility (P = 0.012);.;.;.;
MVP
0.055
MPC
0.21
ClinPred
0.023
T
GERP RS
-3.5
Varity_R
0.052
gMVP
0.36

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: rs751972199; hg19: chr7-100001812; API