12-6836750-C-G

Variant names:

• chr12-6836750-C-G
• rs2269355
• NM_014262.5:c.1459-235C>G

Variant summary

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

The NM_014262.5(P3H3):​c.1459-235C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,026 control chromosomes in the GnomAD database, including 16,878 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 0.47 (16878 hom., cov: 32)
• Consequence: P3H3 NM_014262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 23 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H3	NM_014262.5	MANE Select	c.1459-235C>G		intron	N/A	NP_055077.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H3	ENST00000290510.10	TSL:1 MANE Select	c.1459-235C>G		intron	N/A	ENSP00000478600.1	Q8IVL6-1
	P3H3	ENST00000612048.4	TSL:1	n.992-235C>G		intron	N/A
	P3H3	ENST00000913254.1		c.1489-235C>G		intron	N/A	ENSP00000583313.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70889 AN: 151908 Hom.: 16876 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.467 AC: 70930 AN: 152026 Hom.: 16878 Cov.: 32 AF XY: 0.465 AC XY: 34534 AN XY: 74316

African (AFR) AF: 0.527 AC: 21826 AN: 41444

American (AMR) AF: 0.482 AC: 7363 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1755 AN: 3472

East Asian (EAS) AF: 0.572 AC: 2953 AN: 5162

South Asian (SAS) AF: 0.545 AC: 2632 AN: 4826

European-Finnish (FIN) AF: 0.334 AC: 3536 AN: 10574

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29193 AN: 67954

Other (OTH) AF: 0.498 AC: 1051 AN: 2110

Alfa AF: 0.253 Hom.: 508

Bravo AF: 0.478

Asia WGS AF: 0.555 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.63
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2269355; hg19: chr12-6945914;