12-6838864-T-G

Position:

• chr12-6838864-T-G

Variant summary

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

The ENST00000290510.10(P3H3):​c.1906-136T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 648,778 control chromosomes in the GnomAD database, including 8,443 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 0.15 (1871 hom., cov: 32)
  • Exomes 𝑓: 0.15 (6572 hom.)
• Consequence: P3H3 ENST00000290510.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P3H3	NM_014262.5	c.1906-136T>G		intron_variant		ENST00000290510.10	NP_055077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P3H3	ENST00000290510.10	c.1906-136T>G		intron_variant		1	NM_014262.5	ENSP00000478600	P1
P3H3	ENST00000612048.4	n.1439-136T>G		intron_variant, non_coding_transcript_variant		1
P3H3	ENST00000536140.5	n.2536-136T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22970 AN: 152032 Hom.: 1867 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.150 AC: 74552 AN: 496628 Hom.: 6572 AF XY: 0.149 AC XY: 37170 AN XY: 249518

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.0504

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.151 AC: 22985 AN: 152150 Hom.: 1871 Cov.: 32 AF XY: 0.156 AC XY: 11567 AN XY: 74384

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.0531

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.121

Alfa AF: 0.133 Hom.: 1772

Bravo AF: 0.157

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.6
DANN	Benign	0.81

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: rs4963516; hg19: chr12-6948028; COSMIC: COSV51834901; COSMIC: COSV51834901;