rs543957173

Variant names:

• chr7-76611572-G-A
• rs543957173
• NM_012230.5:c.457C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-76611572-G-A
• chr7-76611572-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_012230.5(POMZP3):​c.457C>T​(p.Leu153Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 149,190 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00023 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: POMZP3 NM_012230.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.207
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.025).
• BP6: Variant 7-76611572-G-A is Benign according to our data. Variant chr7-76611572-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770991.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.207 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMZP3	NM_012230.5	c.457C>T	p.Leu153Leu	synonymous_variant	Exon 6 of 7	ENST00000310842.9	NP_036362.3
POMZP3	NM_152992.4	c.346-1357C>T		intron_variant	Intron 4 of 4		NP_694537.1
LINC03009	NR_029411.1	n.625-14349G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMZP3	ENST00000310842.9	c.457C>T	p.Leu153Leu	synonymous_variant	Exon 6 of 7	1	NM_012230.5	ENSP00000309233.4

Frequencies

GnomAD3 genomes AF: 0.000356 AC: 53 AN: 149076 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000419

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000815 AC: 20 AN: 245438 AF XY: 0.0000904

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000905

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000229 AC: 332 AN: 1449636 Hom.: 3 Cov.: 33 AF XY: 0.000230 AC XY: 166 AN XY: 721164

African (AFR) AF: 0.00 AC: 0 AN: 33244

American (AMR) AF: 0.000408 AC: 18 AN: 44170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25868

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5710

European-Non Finnish (NFE) AF: 0.000263 AC: 290 AN: 1101994

Other (OTH) AF: 0.000334 AC: 20 AN: 59914

GnomAD4 genome AF: 0.000355 AC: 53 AN: 149190 Hom.: 0 Cov.: 23 AF XY: 0.000440 AC XY: 32 AN XY: 72784

African (AFR) AF: 0.000172 AC: 7 AN: 40588

American (AMR) AF: 0.00114 AC: 17 AN: 14866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000212 AC: 1 AN: 4714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000419 AC: 28 AN: 66782

Other (OTH) AF: 0.00 AC: 0 AN: 2040

Alfa AF: 0.000144 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

POMZP3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.92
PhyloP100		0.21
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs543957173; hg19: chr7-76240889; COSMIC: COSV51887467; COSMIC: COSV51887467;