chr12-6839528-A-G

Variant names:

• chr12-6839528-A-G
• rs1047776
• ENST00000612048.4:n.1811A>G

Variant summary

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

The ENST00000612048.4(P3H3):​n.1811A>G variant causes a non coding transcript exon 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 ENST00000612048.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
P3H3	NM_014262.5	c.*67A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000290510.10	NP_055077.2

Ensembl

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

African (AFR) AF: 0.718 AC: 21933 AN: 30532

American (AMR) AF: 0.787 AC: 25814 AN: 32806

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 13140 AN: 23210

East Asian (EAS) AF: 0.986 AC: 34876 AN: 35372

South Asian (SAS) AF: 0.799 AC: 60133 AN: 75264

European-Finnish (FIN) AF: 0.571 AC: 24541 AN: 43002

Middle Eastern (MID) AF: 0.626 AC: 2479 AN: 3960

European-Non Finnish (NFE) AF: 0.641 AC: 675822 AN: 1054808

Other (OTH) AF: 0.674 AC: 37818 AN: 56076

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

African (AFR) AF: 0.716 AC: 29636 AN: 41418

American (AMR) AF: 0.739 AC: 11290 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1988 AN: 3472

East Asian (EAS) AF: 0.976 AC: 5044 AN: 5166

South Asian (SAS) AF: 0.807 AC: 3883 AN: 4814

European-Finnish (FIN) AF: 0.573 AC: 6053 AN: 10562

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42664 AN: 67938

Other (OTH) AF: 0.670 AC: 1413 AN: 2108

Alfa AF: 0.640 Hom.: 31193

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
PhyloP100		-0.027
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1047776; hg19: chr12-6948692;