9-128731344-G-A

Variant names:

• chr9-128731344-G-A
• NM_006336.4:c.2294C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006336.4(ZER1):​c.2294C>T​(p.Ser765Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ZER1 NM_006336.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44

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]

ZDHHC12-DT (HGNC:55873): (ZDHHC12 divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29996276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZER1	NM_006336.4	c.2294C>T	p.Ser765Phe	missense_variant	Exon 16 of 16	ENST00000291900.7	NP_006327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZER1	ENST00000291900.7	c.2294C>T	p.Ser765Phe	missense_variant	Exon 16 of 16	1	NM_006336.4	ENSP00000291900.2
ZDHHC12-DT	ENST00000443631.2	n.202-1498G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2294C>T (p.S765F) alteration is located in exon 16 (coding exon 15) of the ZER1 gene. This alteration results from a C to T substitution at nucleotide position 2294, causing the serine (S) at amino acid position 765 to be replaced by a phenylalanine (F). 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	0.30
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.40
MutPred		0.20		Loss of phosphorylation at S765 (P = 0.0071);
MVP		0.13
MPC		0.27
ClinPred		0.86	D
GERP RS		5.7
Varity_R		0.27
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-131493623;