Genetic Variant NM_006336.4:c.2254G>A (chr9-128731384-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_006336.4(ZER1):c.2254G>A(p.Glu752Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000745 in 134,212 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000075 ( 0 hom., cov: 30)

Consequence

ZER1
NM_006336.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.66

Publications

0 publications found

Variant links:

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]

ZER1 links:

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

ZDHHC12-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZER1	NM_006336.4	MANE Select	c.2254G>A	p.Glu752Lys	missense	Exon 16 of 16	NP_006327.2
ZER1	NM_001375954.1		c.2254G>A	p.Glu752Lys	missense	Exon 16 of 16	NP_001362883.1	Q7Z7L7
ZER1	NM_001375955.1		c.2254G>A	p.Glu752Lys	missense	Exon 16 of 16	NP_001362884.1	Q7Z7L7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZER1	ENST00000291900.7	TSL:1 MANE Select	c.2254G>A	p.Glu752Lys	missense	Exon 16 of 16	ENSP00000291900.2	Q7Z7L7
ZER1	ENST00000960734.1		c.2281G>A	p.Glu761Lys	missense	Exon 16 of 16	ENSP00000630793.1
ZER1	ENST00000873659.1		c.2254G>A	p.Glu752Lys	missense	Exon 18 of 18	ENSP00000543718.1

Frequencies

GnomAD3 genomes

AF:

0.00000745

AC:

AN:

134212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000745

AC:

AN:

134212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64104

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36590

American (AMR)

AF:

0.00

AC:

AN:

12640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3292

East Asian (EAS)

AF:

0.00

AC:

AN:

3826

South Asian (SAS)

AF:

0.00

AC:

AN:

3762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000157

AC:

AN:

63652

Other (OTH)

AF:

0.00

AC:

AN:

1878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.074

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.3

PhyloP100

6.7

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.35

Sift

Benign

0.090

Sift4G

Benign

0.21

Polyphen

0.99

Vest4

0.50

MutPred

0.40

Gain of MoRF binding (P = 0.0019)

MVP

0.14

MPC

0.59

ClinPred

0.92

GERP RS

5.7

Varity_R

0.37

gMVP

0.46

Mutation Taster

=38/62

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over