7-76626043-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_012230.5(POMZP3):c.22C>G(p.Leu8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,598,800 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.011 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 140 hom. )

Consequence

POMZP3
NM_012230.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

Publications

2 publications found

Variant links:

Genes affected

POMZP3 (HGNC:9203): (POM121 and ZP3 fusion) This gene appears to have resulted from a fusion of DNA sequences derived from 2 distinct loci, specifically through the duplication of two internal exons from the POM121 gene and four 3' exons from the ZP3 gene. The 5' end of this gene is similar to the 5` coding region of the POM121 gene which encodes an integral nuclear pore membrane protein. However, the protein encoded by this gene lacks the nuclear pore localization motif. The 3' end of this gene is similar to the last 4 exons of the zona pellucida glycoprotein 3 (ZP3) gene and the encoded protein retains one zona pellucida domain. Multiple protein isoforms are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]

POMZP3 links:

LINC03009 (HGNC:56134): (long intergenic non-protein coding RNA 3009)

LINC03009 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003779769).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0107 (1624/152208) while in subpopulation NFE AF = 0.0158 (1075/68006). AF 95% confidence interval is 0.015. There are 17 homozygotes in GnomAd4. There are 758 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMZP3	NM_012230.5 link	c.22C>G	p.Leu8Val	missense_variant	Exon 2 of 7	ENST00000310842.9	NP_036362.3	Q6PJE2-4
POMZP3	NM_152992.4 link	c.22C>G	p.Leu8Val	missense_variant	Exon 2 of 5		NP_694537.1	Q6PJE2-5
LINC03009	NR_029411.1 link	n.747G>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMZP3	ENST00000310842.9 link	c.22C>G	p.Leu8Val	missense_variant	Exon 2 of 7	1	NM_012230.5	ENSP00000309233.4		Q6PJE2-4

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1623

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00797

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0158

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00161

AC:

405

AN:

250904

AF XY:

0.00142

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00247

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00367

AC:

5305

AN:

1446592

Hom.:

140

Cov.:

AF XY:

0.00362

AC XY:

2606

AN XY:

719984

show subpopulations

African (AFR)

AF:

0.00312

AC:

104

AN:

33310

American (AMR)

AF:

0.00208

AC:

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.00349

AC:

AN:

26094

East Asian (EAS)

AF:

0.000126

AC:

AN:

39696

South Asian (SAS)

AF:

0.000951

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00326

AC:

174

AN:

53324

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00407

AC:

4464

AN:

1097624

Other (OTH)

AF:

0.00484

AC:

290

AN:

59948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

354

707

1061

1414

1768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0107

AC:

1624

AN:

152208

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

758

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00797

AC:

331

AN:

41520

American (AMR)

AF:

0.00693

AC:

106

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.00228

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00386

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0158

AC:

1075

AN:

68006

Other (OTH)

AF:

0.0114

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

154

230

307

384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0108

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 17, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.22C>G (p.L8V) alteration is located in exon 2 (coding exon 1) of the POMZP3 gene. This alteration results from a C to G substitution at nucleotide position 22, causing the leucine (L) at amino acid position 8 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

0.045

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0016

.;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.060

T;T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-3.0

N;N;.

PhyloP100

1.3

PROVEAN

Benign

1.7

N;N;N

REVEL

Benign

0.033

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0020

.;B;.

Vest4

0.22

MVP

0.082

MPC

1.6

ClinPred

0.0049

GERP RS

0.69

PromoterAI

0.020

Neutral

(source)

Varity_R

0.032

gMVP

0.070

Mutation Taster

=99/1

polymorphism

(source)

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

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

7-76626043-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over