chr7-76611492-G-T

Variant names:

• chr7-76611492-G-T
• rs551999681
• NM_012230.5:c.537C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_012230.5(POMZP3):​c.537C>A​(p.Ser179Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000262 in 1,604,242 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000028 (2 hom.)
• Consequence: POMZP3 NM_012230.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0500
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02577883).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.537C>A	p.Ser179Arg	missense	Exon 6 of 7	NP_036362.3
	POMZP3	NM_152992.4		c.346-1277C>A		intron	N/A	NP_694537.1	Q6PJE2-5
	LINC03009	NR_029411.1		n.625-14429G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMZP3	ENST00000310842.9	TSL:1 MANE Select	c.537C>A	p.Ser179Arg	missense	Exon 6 of 7	ENSP00000309233.4	Q6PJE2-4
	LINC03009	ENST00000418663.5	TSL:1	n.606-14429G>T		intron	N/A
	LINC03009	ENST00000450661.1	TSL:1	n.605-14429G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150518 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000644 AC: 16 AN: 248372 AF XY: 0.0000521

Gnomad AFR exome AF: 0.00

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 AF: 0.0000275 AC: 40 AN: 1453610 Hom.: 2 Cov.: 61 AF XY: 0.0000304 AC XY: 22 AN XY: 723246

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000406 AC: 35 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104616

Other (OTH) AF: 0.0000832 AC: 5 AN: 60112

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150632 Hom.: 0 Cov.: 29 AF XY: 0.0000272 AC XY: 2 AN XY: 73590

African (AFR) AF: 0.00 AC: 0 AN: 40992

American (AMR) AF: 0.00 AC: 0 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000418 AC: 2 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67372

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.0000509 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000908 AC: 11

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	0.18
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.6
DANN	Benign	0.86
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0064	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L
PhyloP100		-0.050
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.059
Sift	Benign	0.67	T
Sift4G	Benign	0.36	T
Polyphen		0.041	B
Vest4		0.12
MutPred		0.37		Gain of solvent accessibility (P = 0.0055)
MVP		0.082
MPC		0.010
ClinPred		0.0090	T
GERP RS		0.79
Varity_R		0.058
gMVP		0.34
Mutation Taster		=88/12	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: rs551999681; hg19: chr7-76240809;