12-6838568-C-T

Variant names:

• chr12-6838568-C-T
• rs3759348
• NM_014262.5:c.1906-432C>T

Variant summary

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

The NM_014262.5(P3H3):​c.1906-432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,906 control chromosomes in the GnomAD database, including 6,594 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 0.29 (6594 hom., cov: 32)
• Consequence: P3H3 NM_014262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H3	NM_014262.5	c.1906-432C>T		intron_variant	Intron 13 of 14	ENST00000290510.10	NP_055077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H3	ENST00000290510.10	c.1906-432C>T		intron_variant	Intron 13 of 14	1	NM_014262.5	ENSP00000478600.1
P3H3	ENST00000612048.4	n.1439-432C>T		intron_variant	Intron 12 of 13	1
P3H3	ENST00000536140.5	n.2536-432C>T		intron_variant	Intron 14 of 15	2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44176 AN: 151788 Hom.: 6592 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.291 AC: 44188 AN: 151906 Hom.: 6594 Cov.: 32 AF XY: 0.291 AC XY: 21567 AN XY: 74216

African (AFR) AF: 0.259 AC: 10719 AN: 41398

American (AMR) AF: 0.324 AC: 4944 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3468

East Asian (EAS) AF: 0.371 AC: 1919 AN: 5170

South Asian (SAS) AF: 0.332 AC: 1594 AN: 4800

European-Finnish (FIN) AF: 0.277 AC: 2925 AN: 10552

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19927 AN: 67938

Other (OTH) AF: 0.320 AC: 677 AN: 2114

Alfa AF: 0.294 Hom.: 7821

Bravo AF: 0.292

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.90
DANN	Benign	0.72
PhyloP100		-1.3
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: rs3759348; hg19: chr12-6947732;