Variant 7-76611810-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012230.5(POMZP3):c.349T>C(p.Tyr117His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000547 in 1,573,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000055 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

POMZP3
NM_012230.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

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 made for transcript

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=0.2700395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
POMZP3	NM_012230.5 linkuse as main transcript	c.349T>C	p.Tyr117His	missense_variant	5/7	ENST00000310842.9	NP_036362.3
LINC03009	NR_029411.1 linkuse as main transcript	n.625-14111A>G		intron_variant, non_coding_transcript_variant
POMZP3	NM_152992.4 linkuse as main transcript	c.346-1595T>C		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.349T>C	p.Tyr117His	missense_variant	5/7	1	NM_012230.5	ENSP00000309233	P1	Q6PJE2-4
LINC03009	ENST00000418663.5 linkuse as main transcript	n.606-14111A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000546

AC:

AN:

146390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000588

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000193

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000601

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000817

AC:

AN:

232658

Hom.:

AF XY:

0.0000799

AC XY:

AN XY:

125164

show subpopulations

Gnomad AFR exome

AF:

0.0000686

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000345

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000525

Gnomad NFE exome

AF:

0.0000391

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1427026

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

709108

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000241

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000417

Gnomad4 NFE exome

AF:

0.0000415

Gnomad4 OTH exome

AF:

0.0000339

GnomAD4 genome

AF:

0.0000546

AC:

AN:

146496

Hom.:

Cov.:

AF XY:

0.0000420

AC XY:

AN XY:

71458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000588

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000193

Gnomad4 NFE

AF:

0.0000601

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000316

Hom.:

ESP6500AA

AF:

0.000231

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000100

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

Apr 15, 2024

The c.349T>C (p.Y117H) alteration is located in exon 5 (coding exon 4) of the POMZP3 gene. This alteration results from a T to C substitution at nucleotide position 349, causing the tyrosine (Y) at amino acid position 117 to be replaced by a histidine (H). 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

0.46

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

D;.

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.042

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.27

T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Pathogenic

3.5

M;.

MutationTaster

Benign

0.99

D;D;D;D

PROVEAN

Uncertain

-3.5

D;N

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.20

T;.

Polyphen

1.0

D;.

Vest4

0.71

MVP

0.13

MPC

3.3

ClinPred

0.91

GERP RS

0.79

Varity_R

0.60

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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