NM_006336.4:c.1706A>G

Variant names:

• chr9-128741566-T-C
• rs1564395378
• NM_006336.4:c.1706A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006336.4(ZER1):​c.1706A>G​(p.Asn569Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZER1 NM_006336.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

ZER1 (HGNC:30960): (zyg-11 related cell cycle regulator) This gene encodes a subunit of an E3 ubiquitin ligase complex that may be involved in meiosis. The encoded protein contains three leucine-rich repeat motifs. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0971109).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006336.4. 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
	ZER1	NM_006336.4	MANE Select	c.1706A>G	p.Asn569Ser	missense	Exon 11 of 16	NP_006327.2
	ZER1	NM_001375954.1		c.1706A>G	p.Asn569Ser	missense	Exon 11 of 16	NP_001362883.1	Q7Z7L7
	ZER1	NM_001375955.1		c.1706A>G	p.Asn569Ser	missense	Exon 11 of 16	NP_001362884.1	Q7Z7L7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZER1	ENST00000291900.7	TSL:1 MANE Select	c.1706A>G	p.Asn569Ser	missense	Exon 11 of 16	ENSP00000291900.2	Q7Z7L7
	ZER1	ENST00000960734.1		c.1733A>G	p.Asn578Ser	missense	Exon 11 of 16	ENSP00000630793.1
	ZER1	ENST00000873659.1		c.1706A>G	p.Asn569Ser	missense	Exon 13 of 18	ENSP00000543718.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.055
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.14	N
PhyloP100		1.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.032
Sift	Benign	0.27	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.40		Loss of catalytic residue at N569 (P = 0.0317)
MVP		0.068
MPC		0.85
ClinPred		0.10	T
GERP RS		1.5
Varity_R		0.044
gMVP		0.016
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1564395378; hg19: chr9-131503845;