7-76618283-A-G

Variant names:

• chr7-76618283-A-G
• rs1815359268
• NM_012230.5:c.245T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012230.5(POMZP3):​c.245T>C​(p.Leu82Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: POMZP3 NM_012230.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00400
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32453492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMZP3	NM_012230.5	c.245T>C	p.Leu82Pro	missense_variant	Exon 4 of 7	ENST00000310842.9	NP_036362.3
POMZP3	NM_152992.4	c.245T>C	p.Leu82Pro	missense_variant	Exon 4 of 5		NP_694537.1
LINC03009	NR_029411.1	n.625-7638A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMZP3	ENST00000310842.9	c.245T>C	p.Leu82Pro	missense_variant	Exon 4 of 7	1	NM_012230.5	ENSP00000309233.4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.245T>C (p.L82P) alteration is located in exon 4 (coding exon 3) of the POMZP3 gene. This alteration results from a T to C substitution at nucleotide position 245, causing the leucine (L) at amino acid position 82 to be replaced by a proline (P). 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	0.45
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Uncertain	0.44	.;T;.
Eigen	Benign	0.086
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Pathogenic	3.0	M;M;.
PhyloP100		-0.0040
PROVEAN	Benign	0.49	N;D;D
REVEL	Benign	0.23
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.14	T;T;.
Polyphen		1.0	.;D;.
Vest4		0.23
MutPred		0.49		Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);.;
MVP		0.62
MPC		3.7
ClinPred		0.47	T
PromoterAI		0.0042	Neutral
Varity_R		0.43
gMVP		0.31
Mutation Taster		=76/24	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: rs1815359268; hg19: chr7-76247600;