chr12-6839528-A-G

Position:

• chr12-6839528-A-G

Variant summary

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

The ENST00000290510.10(P3H3):​c.*67A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 1,506,996 control chromosomes in the GnomAD database, including 336,065 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 0.68 (35269 hom., cov: 31)
  • Exomes 𝑓: 0.66 (300796 hom.)
• Consequence: P3H3 ENST00000290510.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

Genes affected

P3H3 (HGNC:19318): (prolyl 3-hydroxylase 3) The protein encoded by this gene belongs to the leprecan family of proteoglycans, which function as collagen prolyl hydroxylases that are required for proper collagen biosynthesis, folding and assembly. This protein, like other family members, is thought to reside in the endoplasmic reticulum. Epigenetic inactivation of this gene is associated with breast and other cancers, suggesting that it may function as a tumor suppressor. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P3H3	NM_014262.5	c.*67A>G		3_prime_UTR_variant	15/15	ENST00000290510.10	NP_055077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P3H3	ENST00000290510.10	c.*67A>G		3_prime_UTR_variant	15/15	1	NM_014262.5	ENSP00000478600	P1
P3H3	ENST00000612048.4	n.1811A>G		non_coding_transcript_exon_variant	14/14	1
P3H3	ENST00000536140.5	n.2908A>G		non_coding_transcript_exon_variant	16/16	2

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102688 AN: 151848 Hom.: 35238 Cov.: 31

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.666

GnomAD4 exome AF: 0.662 AC: 896556 AN: 1355030 Hom.: 300796 Cov.: 25 AF XY: 0.665 AC XY: 442851 AN XY: 665694

Gnomad4 AFR exome AF: 0.718

Gnomad4 AMR exome AF: 0.787

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.986

Gnomad4 SAS exome AF: 0.799

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.641

Gnomad4 OTH exome AF: 0.674

GnomAD4 genome AF: 0.676 AC: 102768 AN: 151966 Hom.: 35269 Cov.: 31 AF XY: 0.680 AC XY: 50475 AN XY: 74274

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.670

Alfa AF: 0.631 Hom.: 21054

Bravo AF: 0.692

Asia WGS AF: 0.870 AC: 3021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1047776; hg19: chr12-6948692;