7-76611513-C-G

Variant names:

• chr7-76611513-C-G
• rs770531972
• NM_012230.5:c.516G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012230.5(POMZP3):​c.516G>C​(p.Arg172Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: POMZP3 NM_012230.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13629973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMZP3	NM_012230.5	c.516G>C	p.Arg172Ser	missense_variant	Exon 6 of 7	ENST00000310842.9	NP_036362.3
POMZP3	NM_152992.4	c.346-1298G>C		intron_variant	Intron 4 of 4		NP_694537.1
LINC03009	NR_029411.1	n.625-14408C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMZP3	ENST00000310842.9	c.516G>C	p.Arg172Ser	missense_variant	Exon 6 of 7	1	NM_012230.5	ENSP00000309233.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.7
DANN	Benign	0.93
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.9
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.062
Sift	Benign	0.20	T
Sift4G	Benign	0.068	T
Polyphen		0.77	P
Vest4		0.32
MutPred		0.24		Gain of relative solvent accessibility (P = 0.0166);
MVP		0.093
MPC		0.017
ClinPred		0.41	T
GERP RS		0.79
Varity_R		0.15
gMVP		0.55
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs770531972; hg19: chr7-76240830;