dbSNP rs373450388: ZCWPW1:p.Arg480Pro (chr7-100402551-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001386010.1(ZCWPW1):c.1439G>C(p.Arg480Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R480Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZCWPW1
NM_001386010.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.642

Publications

0 publications found

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]

ZCWPW1 links:

ENSG00000289690 (HGNC:):

ENSG00000289690 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026221305).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386010.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZCWPW1	NM_001386010.1	MANE Select	c.1439G>C	p.Arg480Pro	missense	Exon 16 of 18	NP_001372939.1	A0A804HK41
ZCWPW1	NM_017984.6		c.1436G>C	p.Arg479Pro	missense	Exon 16 of 18	NP_060454.3
ZCWPW1	NM_001386016.1		c.1439G>C	p.Arg480Pro	missense	Exon 16 of 18	NP_001372945.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZCWPW1	ENST00000684423.1	MANE Select	c.1439G>C	p.Arg480Pro	missense	Exon 16 of 18	ENSP00000507762.1	A0A804HK41
ZCWPW1	ENST00000398027.6	TSL:1	c.1436G>C	p.Arg479Pro	missense	Exon 16 of 18	ENSP00000381109.2	Q9H0M4-1
ZCWPW1	ENST00000490721.5	TSL:1	c.1076G>C	p.Arg359Pro	missense	Exon 13 of 14	ENSP00000419187.1	Q9H0M4-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111994

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.1

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.00080

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.56

M_CAP

Benign

0.0033

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

PhyloP100

0.64

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.15

REVEL

Benign

0.046

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.085

MutPred

0.32

Loss of MoRF binding (P = 0.0231)

MVP

0.030

MPC

0.21

ClinPred

0.055

GERP RS

1.5

Varity_R

0.081

gMVP

0.48

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.20

Position offset: 25

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over