NM_001386010.1:c.1343A>G

Variant names:

• chr7-100403764-T-C
• NM_001386010.1:c.1343A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001386010.1(ZCWPW1):​c.1343A>G​(p.Asn448Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZCWPW1 NM_001386010.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.182
• 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: 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=0.05770138).

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.1343A>G	p.Asn448Ser	missense	Exon 15 of 18	NP_001372939.1	A0A804HK41
	ZCWPW1	NM_017984.6		c.1340A>G	p.Asn447Ser	missense	Exon 15 of 18	NP_060454.3
	ZCWPW1	NM_001386016.1		c.1343A>G	p.Asn448Ser	missense	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.1343A>G	p.Asn448Ser	missense	Exon 15 of 18	ENSP00000507762.1	A0A804HK41
	ZCWPW1	ENST00000398027.6	TSL:1	c.1340A>G	p.Asn447Ser	missense	Exon 15 of 18	ENSP00000381109.2	Q9H0M4-1
	ZCWPW1	ENST00000490721.5	TSL:1	c.980A>G	p.Asn327Ser	missense	Exon 12 of 14	ENSP00000419187.1	Q9H0M4-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461786 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727196

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111974

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.1
DANN	Benign	0.80
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.18
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.014
Sift	Benign	0.12	T
Sift4G	Benign	0.092	T
Polyphen		0.051	B
Vest4		0.065
MutPred		0.13		Gain of phosphorylation at N447 (P = 0.0069)
MVP		0.030
MPC		0.13
ClinPred		0.094	T
GERP RS		2.9
Varity_R		0.060
gMVP		0.11
Mutation Taster		=96/4	polymorphism

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

hg19: chr7-100001387;