rs1754228

Positions:

• chr7-76625767-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMZP3	NM_012230.5	c.66-84T>C		intron_variant		ENST00000310842.9	NP_036362.3
LINC03009	NR_029411.1	n.625-154A>G		intron_variant, non_coding_transcript_variant
POMZP3	NM_152992.4	c.66-84T>C		intron_variant			NP_694537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMZP3	ENST00000310842.9	c.66-84T>C		intron_variant		1	NM_012230.5	ENSP00000309233	P1
LINC03009	ENST00000418663.5	n.606-154A>G		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.162

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

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.180

Alfa AF: 0.197 Hom.: 314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.8
DANN	Benign	0.18

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

Publications

LitVar

Other links and lift over

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