12-6837196-C-T

Position:

• chr12-6837196-C-T

Variant summary

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

The NM_014262.5(P3H3):​c.1560+110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,037,460 control chromosomes in the GnomAD database, including 43,785 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 (6565 hom., cov: 32)
  • Exomes 𝑓: 0.29 (37220 hom.)
• Consequence: P3H3 NM_014262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44

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 = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P3H3	NM_014262.5	c.1560+110C>T		intron_variant		ENST00000290510.10	NP_055077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P3H3	ENST00000290510.10	c.1560+110C>T		intron_variant		1	NM_014262.5	ENSP00000478600.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44083 AN: 151968 Hom.: 6564 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.286 AC: 253033 AN: 885374 Hom.: 37220 Cov.: 12 AF XY: 0.288 AC XY: 129215 AN XY: 448798

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.332

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.290 AC: 44103 AN: 152086 Hom.: 6565 Cov.: 32 AF XY: 0.290 AC XY: 21584 AN XY: 74346

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.309

Alfa AF: 0.290 Hom.: 8344

Bravo AF: 0.292

Asia WGS AF: 0.325 AC: 1127 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	0.14
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10849527; hg19: chr12-6946360; COSMIC: COSV51835999; COSMIC: COSV51835999;