dbSNP rs1476679: ZCWPW1:c.1069-25G>T (chr7-100406823-C-A) – 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.1069-25G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZCWPW1
NM_001386010.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.43

Publications

150 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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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	Effect	Exon Rank	Protein
ZCWPW1	NM_001386010.1	MANE Select	c.1069-25G>T	intron	N/A	NP_001372939.1
ZCWPW1	NM_017984.6		c.1066-25G>T	intron	N/A	NP_060454.3
ZCWPW1	NM_001386016.1		c.1069-25G>T	intron	N/A	NP_001372945.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZCWPW1	ENST00000684423.1	MANE Select	c.1069-25G>T	intron	N/A	ENSP00000507762.1
ZCWPW1	ENST00000398027.6	TSL:1	c.1066-25G>T	intron	N/A	ENSP00000381109.2
ZCWPW1	ENST00000490721.5	TSL:1	c.706-25G>T	intron	N/A	ENSP00000419187.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

247862

AF XY:

0.00000743

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453100

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723524

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33282

American (AMR)

AF:

0.00

AC:

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.00

AC:

AN:

86032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1104366

Other (OTH)

AF:

0.00

AC:

AN:

60050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.068

(source)

DANN

Benign

0.68

PhyloP100

-2.4

BranchPoint Hunter

0.0

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

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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