NM_012230.5:c.66-84T>C

Variant names:

• chr7-76625767-A-G
• rs1754228
• NM_012230.5:c.66-84T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012230.5(POMZP3):​c.66-84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,388,642 control chromosomes in the GnomAD database, including 20,984 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (2667 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18317 hom.)
• Consequence: POMZP3 NM_012230.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

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.66-84T>C		intron	N/A	NP_036362.3
	POMZP3	NM_152992.4		c.66-84T>C		intron	N/A	NP_694537.1	Q6PJE2-5
	LINC03009	NR_029411.1		n.625-154A>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.66-84T>C		intron	N/A	ENSP00000309233.4	Q6PJE2-4
	LINC03009	ENST00000418663.5	TSL:1	n.606-154A>G		intron	N/A
	LINC03009	ENST00000450661.1	TSL:1	n.605-154A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28236 AN: 151178 Hom.: 2671 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.154 AC: 191077 AN: 1237348 Hom.: 18317 Cov.: 31 AF XY: 0.159 AC XY: 97716 AN XY: 616504

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.110 AC: 3297 AN: 29956

American (AMR) AF: 0.206 AC: 6882 AN: 33404

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4121 AN: 21522

East Asian (EAS) AF: 0.251 AC: 9494 AN: 37876

South Asian (SAS) AF: 0.225 AC: 16135 AN: 71556

European-Finnish (FIN) AF: 0.153 AC: 7788 AN: 50944

Middle Eastern (MID) AF: 0.142 AC: 738 AN: 5200

European-Non Finnish (NFE) AF: 0.144 AC: 134115 AN: 934536

Other (OTH) AF: 0.162 AC: 8507 AN: 52354

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.187 AC: 28251 AN: 151294 Hom.: 2667 Cov.: 32 AF XY: 0.185 AC XY: 13656 AN XY: 73908

African (AFR) AF: 0.141 AC: 5804 AN: 41306

American (AMR) AF: 0.202 AC: 3060 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 800 AN: 3444

East Asian (EAS) AF: 0.241 AC: 1228 AN: 5096

South Asian (SAS) AF: 0.265 AC: 1265 AN: 4774

European-Finnish (FIN) AF: 0.151 AC: 1593 AN: 10544

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13949 AN: 67678

Other (OTH) AF: 0.180 AC: 375 AN: 2088

Alfa AF: 0.197 Hom.: 314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.8
DANN	Benign	0.18
PhyloP100		-1.1
PromoterAI		0.040	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs1754228; hg19: chr7-76255084; COSMIC: COSV51885705; COSMIC: COSV51885705;