Variant 7-76611743-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_012230.5(POMZP3):c.416C>G(p.Ser139Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,534,684 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000065 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00013 ( 16 hom. )

Consequence

POMZP3
NM_012230.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
POMZP3	NM_012230.5 linkuse as main transcript	c.416C>G	p.Ser139Cys	missense_variant	5/7	ENST00000310842.9	NP_036362.3
LINC03009	NR_029411.1 linkuse as main transcript	n.625-14178G>C		intron_variant, non_coding_transcript_variant
POMZP3	NM_152992.4 linkuse as main transcript	c.346-1528C>G		intron_variant			NP_694537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMZP3	ENST00000310842.9 linkuse as main transcript	c.416C>G	p.Ser139Cys	missense_variant	5/7	1	NM_012230.5	ENSP00000309233	P1	Q6PJE2-4
LINC03009	ENST00000418663.5 linkuse as main transcript	n.606-14178G>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000649

AC:

AN:

138702

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000714

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000990

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000111

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000468

AC:

AN:

235080

Hom.:

AF XY:

0.0000395

AC XY:

AN XY:

126578

show subpopulations

Gnomad AFR exome

AF:

0.0000674

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000870

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.000125

AC:

175

AN:

1395982

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

694958

show subpopulations

Gnomad4 AFR exome

AF:

0.0000623

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000157

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.0000649

AC:

AN:

138702

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

67542

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000714

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000990

Gnomad4 NFE

AF:

0.000111

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000335

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 04, 2024

The c.416C>G (p.S139C) alteration is located in exon 5 (coding exon 4) of the POMZP3 gene. This alteration results from a C to G substitution at nucleotide position 416, causing the serine (S) at amino acid position 139 to be replaced by a cysteine (C). 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

Uncertain

0.44

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.77

D;.

Eigen

Uncertain

0.26

Eigen_PC

Benign

-0.0038

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.0072

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Uncertain

0.43

MutationAssessor

Pathogenic

3.4

M;.

MutationTaster

Benign

0.92

D;D;D;D

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0050

D;.

Polyphen

1.0

D;.

Vest4

0.50

MVP

0.42

MPC

0.064

ClinPred

0.65

GERP RS

0.79

Varity_R

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over