chr7-76611489-C-G

Variant names:

• chr7-76611489-C-G
• rs756586339
• NM_012230.5:c.540G>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.540G>C​(p.Gln180His) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POMZP3 NM_012230.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.147
• 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=0.14849806).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012230.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMZP3	NM_012230.5	MANE Select	c.540G>C	p.Gln180His	missense	Exon 6 of 7	NP_036362.3
	POMZP3	NM_152992.4		c.346-1274G>C		intron	N/A	NP_694537.1	Q6PJE2-5
	LINC03009	NR_029411.1		n.625-14432C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMZP3	ENST00000310842.9	TSL:1 MANE Select	c.540G>C	p.Gln180His	missense	Exon 6 of 7	ENSP00000309233.4	Q6PJE2-4
	LINC03009	ENST00000418663.5	TSL:1	n.606-14432C>G		intron	N/A
	LINC03009	ENST00000450661.1	TSL:1	n.605-14432C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000807 AC: 2 AN: 247856 AF XY: 0.00000746

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000138 AC: 2 AN: 1453436 Hom.: 0 Cov.: 60 AF XY: 0.00000138 AC XY: 1 AN XY: 723186

African (AFR) AF: 0.0000299 AC: 1 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104514

Other (OTH) AF: 0.00 AC: 0 AN: 60104

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000826 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.15
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.079
Sift	Benign	0.13	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.14
MutPred		0.24		Gain of sheet (P = 0.0827)
MVP		0.12
MPC		0.014
ClinPred		0.074	T
GERP RS		-0.35
Varity_R		0.054
gMVP		0.50
Mutation Taster		=100/0	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: rs756586339; hg19: chr7-76240806;