7-100406823-C-T

Position:

• chr7-100406823-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386010.1(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 NM_001386010.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 0 / 10). 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCWPW1	NM_001386010.1	c.1069-25G>A		intron_variant		ENST00000684423.1	NP_001372939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCWPW1	ENST00000684423.1	c.1069-25G>A		intron_variant			NM_001386010.1	ENSP00000507762.1
ENSG00000289690	ENST00000695708.1	c.-1208+7211C>T		intron_variant				ENSP00000512108.1

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

GnomAD3 exomes AF: 0.736 AC: 182477 AN: 247862 Hom.: 67678 AF XY: 0.735 AC XY: 98878 AN XY: 134504

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 SAS exome AF: 0.775

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

Gnomad4 AFR exome AF: 0.950

Gnomad4 AMR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.783

Gnomad4 EAS exome AF: 0.680

Gnomad4 SAS exome AF: 0.771

Gnomad4 FIN exome AF: 0.724

Gnomad4 NFE exome AF: 0.695

Gnomad4 OTH exome AF: 0.727

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

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.776

Alfa AF: 0.722 Hom.: 70660

Bravo AF: 0.786

Asia WGS AF: 0.711 AC: 2473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.14
DANN	Benign	0.71
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

LitVar

Other links and lift over

dbSNP: rs1476679; hg19: chr7-100004446;