9-128741566-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 16/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZER1	NM_006336.4	c.1706A>G	p.Asn569Ser	missense_variant	Exon 11 of 16	ENST00000291900.7	NP_006327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZER1	ENST00000291900.7	c.1706A>G	p.Asn569Ser	missense_variant	Exon 11 of 16	1	NM_006336.4	ENSP00000291900.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1706A>G (p.N569S) alteration is located in exon 11 (coding exon 10) of the ZER1 gene. This alteration results from a A to G substitution at nucleotide position 1706, causing the asparagine (N) at amino acid position 569 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1564395378; hg19: chr9-131503845;