rs757466499

Variant names:

• chr7-100403744-C-A
• rs757466499
• NM_001386010.1:c.1363G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-100403744-C-A
• chr7-100403744-C-G
• chr7-100403744-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001386010.1(ZCWPW1):​c.1363G>T​(p.Glu455*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,798 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZCWPW1 NM_001386010.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCWPW1	NM_001386010.1	MANE Select	c.1363G>T	p.Glu455*	stop_gained	Exon 15 of 18	NP_001372939.1	A0A804HK41
	ZCWPW1	NM_017984.6		c.1360G>T	p.Glu454*	stop_gained	Exon 15 of 18	NP_060454.3
	ZCWPW1	NM_001386016.1		c.1363G>T	p.Glu455*	stop_gained	Exon 15 of 18	NP_001372945.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCWPW1	ENST00000684423.1	MANE Select	c.1363G>T	p.Glu455*	stop_gained	Exon 15 of 18	ENSP00000507762.1	A0A804HK41
	ZCWPW1	ENST00000398027.6	TSL:1	c.1360G>T	p.Glu454*	stop_gained	Exon 15 of 18	ENSP00000381109.2	Q9H0M4-1
	ZCWPW1	ENST00000490721.5	TSL:1	c.1000G>T	p.Glu334*	stop_gained	Exon 12 of 14	ENSP00000419187.1	Q9H0M4-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461798 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727200

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.028	N
PhyloP100		1.2
Vest4		0.30
ClinPred		0.76	D
GERP RS		2.3
Mutation Taster		=90/110	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs757466499; hg19: chr7-100001367;