7-76626174-C-T

Position:

• chr7-76626174-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012230.5(POMZP3):​c.-110G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,584,220 control chromosomes in the GnomAD database, including 102,505 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 0.37 (10532 hom., cov: 30)
  • Exomes 𝑓: 0.35 (91973 hom.)
• Consequence: POMZP3 NM_012230.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMZP3	NM_012230.5	c.-110G>A		5_prime_UTR_variant	2/7	ENST00000310842.9
LINC03009	NR_029411.1	n.878C>T		non_coding_transcript_exon_variant	3/3
POMZP3	NM_152992.4	c.-110G>A		5_prime_UTR_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMZP3	ENST00000310842.9	c.-110G>A		5_prime_UTR_variant	2/7	1	NM_012230.5	P1
LINC03009	ENST00000418663.5	n.859C>T		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55713 AN: 151464 Hom.: 10516 Cov.: 30

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.354 AC: 506817 AN: 1432644 Hom.: 91973 Cov.: 40 AF XY: 0.353 AC XY: 251010 AN XY: 710682

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.364

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.368 AC: 55755 AN: 151576 Hom.: 10532 Cov.: 30 AF XY: 0.362 AC XY: 26788 AN XY: 74090

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.404

Alfa AF: 0.153 Hom.: 187

Bravo AF: 0.379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1056119; hg19: chr7-76255491; COSMIC: COSV51885371; COSMIC: COSV51885371;