9-128733484-G-C

Variant names:

• chr9-128733484-G-C
• NM_006336.4:c.2185C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006336.4(ZER1):​c.2185C>G​(p.Leu729Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZER1 NM_006336.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZER1	NM_006336.4	c.2185C>G	p.Leu729Val	missense_variant	Exon 15 of 16	ENST00000291900.7	NP_006327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZER1	ENST00000291900.7	c.2185C>G	p.Leu729Val	missense_variant	Exon 15 of 16	1	NM_006336.4	ENSP00000291900.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2185C>G (p.L729V) alteration is located in exon 15 (coding exon 14) of the ZER1 gene. This alteration results from a C to G substitution at nucleotide position 2185, causing the leucine (L) at amino acid position 729 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.19
Sift	Benign	0.10	T
Sift4G	Benign	0.57	T
Polyphen		0.99	D
Vest4		0.75
MutPred		0.28		Gain of MoRF binding (P = 0.0806);
MVP		0.19
MPC		0.52
ClinPred		0.91	D
GERP RS		5.8
Varity_R		0.30
gMVP		0.52

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-131495763;