12-6838636-T-C

Variant names:

• chr12-6838636-T-C
• rs4963517
• NM_014262.5:c.1906-364T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014262.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H3	NM_014262.5	MANE Select	c.1906-364T>C		intron	N/A	NP_055077.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H3	ENST00000290510.10	TSL:1 MANE Select	c.1906-364T>C		intron	N/A	ENSP00000478600.1
	P3H3	ENST00000612048.4	TSL:1	n.1439-364T>C		intron	N/A
	P3H3	ENST00000536140.5	TSL:2	n.2536-364T>C		intron	N/A

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

African (AFR) AF: 0.713 AC: 29425 AN: 41290

American (AMR) AF: 0.712 AC: 10857 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1915 AN: 3464

East Asian (EAS) AF: 0.976 AC: 5035 AN: 5158

South Asian (SAS) AF: 0.790 AC: 3784 AN: 4788

European-Finnish (FIN) AF: 0.521 AC: 5472 AN: 10508

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38847 AN: 67852

Other (OTH) AF: 0.646 AC: 1360 AN: 2106

Alfa AF: 0.600 Hom.: 110900

Bravo AF: 0.661

Asia WGS AF: 0.862 AC: 2993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.70
PhyloP100		-0.019
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: rs4963517; hg19: chr12-6947800;