12-6838636-T-C

Position:

• chr12-6838636-T-C

Variant summary

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

The NM_014262.5(P3H3):​c.1906-364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,612 control chromosomes in the GnomAD database, including 32,072 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 0.64 (32072 hom., cov: 29)
• Consequence: P3H3 NM_014262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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]

P3H3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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.1906-364T>C		intron_variant		ENST00000290510.10	NP_055077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P3H3	ENST00000290510.10	c.1906-364T>C		intron_variant		1	NM_014262.5	ENSP00000478600.1
P3H3	ENST00000612048.4	n.1439-364T>C		intron_variant		1
P3H3	ENST00000536140.5	n.2536-364T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97445 AN: 151494 Hom.: 32042 Cov.: 29

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.643 AC: 97521 AN: 151612 Hom.: 32072 Cov.: 29 AF XY: 0.647 AC XY: 47872 AN XY: 74042

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.646

Alfa AF: 0.594 Hom.: 49335

Bravo AF: 0.661

Asia WGS AF: 0.862 AC: 2993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.70
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: rs4963517; hg19: chr12-6947800;