7-100406823-C-T

Variant names:

• chr7-100406823-C-T
• rs1476679
• NM_001386010.1:c.1069-25G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000684423.1(ZCWPW1):​c.1069-25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,603,952 control chromosomes in the GnomAD database, including 415,635 homozygotes. 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: 𝑓 0.78 (46839 hom., cov: 29)
  • Exomes 𝑓: 0.71 (368796 hom.)
• Consequence: ZCWPW1 ENST00000684423.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43
• Publications: 150 publications found

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]

ENSG00000289690 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000684423.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCWPW1	NM_001386010.1	MANE Select	c.1069-25G>A		intron	N/A	NP_001372939.1
	ZCWPW1	NM_017984.6		c.1066-25G>A		intron	N/A	NP_060454.3
	ZCWPW1	NM_001386016.1		c.1069-25G>A		intron	N/A	NP_001372945.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118208 AN: 151898 Hom.: 46789 Cov.: 29

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.775

GnomAD2 exomes AF: 0.736 AC: 182477 AN: 247862 AF XY: 0.735

Gnomad AFR exome AF: 0.946

Gnomad AMR exome AF: 0.749

Gnomad ASJ exome AF: 0.783

Gnomad EAS exome AF: 0.667

Gnomad FIN exome AF: 0.721

Gnomad NFE exome AF: 0.703

Gnomad OTH exome AF: 0.736

GnomAD4 exome AF: 0.711 AC: 1032025 AN: 1451936 Hom.: 368796 Cov.: 26 AF XY: 0.713 AC XY: 515733 AN XY: 722986

African (AFR) AF: 0.950 AC: 31598 AN: 33276

American (AMR) AF: 0.750 AC: 33439 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 20395 AN: 26060

East Asian (EAS) AF: 0.680 AC: 26930 AN: 39632

South Asian (SAS) AF: 0.771 AC: 66327 AN: 85994

European-Finnish (FIN) AF: 0.724 AC: 38576 AN: 53254

Middle Eastern (MID) AF: 0.758 AC: 4367 AN: 5758

European-Non Finnish (NFE) AF: 0.695 AC: 766764 AN: 1103344

Other (OTH) AF: 0.727 AC: 43629 AN: 60006

GnomAD4 genome AF: 0.778 AC: 118317 AN: 152016 Hom.: 46839 Cov.: 29 AF XY: 0.778 AC XY: 57788 AN XY: 74278

African (AFR) AF: 0.939 AC: 38963 AN: 41512

American (AMR) AF: 0.767 AC: 11715 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2725 AN: 3472

East Asian (EAS) AF: 0.671 AC: 3454 AN: 5150

South Asian (SAS) AF: 0.764 AC: 3677 AN: 4810

European-Finnish (FIN) AF: 0.725 AC: 7660 AN: 10560

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47594 AN: 67934

Other (OTH) AF: 0.776 AC: 1638 AN: 2110

Alfa AF: 0.731 Hom.: 166224

Bravo AF: 0.786

Asia WGS AF: 0.711 AC: 2473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.14
DANN	Benign	0.71
PhyloP100		-2.4
BranchPoint Hunter		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1476679; hg19: chr7-100004446;