12-6829708-C-T

Position:

• chr12-6829708-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.499-151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 744,788 control chromosomes in the GnomAD database, including 43,776 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 0.40 (16526 hom., cov: 31)
  • Exomes 𝑓: 0.28 (27250 hom.)
• Consequence: P3H3 NM_014262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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]

GPR162 (HGNC:16693): (G protein-coupled receptor 162) This gene was identified upon genomic analysis of a gene-dense region at human chromosome 12p13. It appears to be mainly expressed in the brain; however, its function is not known. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P3H3	NM_014262.5	c.499-151C>T		intron_variant		ENST00000290510.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P3H3	ENST00000290510.10	c.499-151C>T		intron_variant		1	NM_014262.5	P1
GPR162	ENST00000545321.1	c.570-151C>T		intron_variant		2
P3H3	ENST00000536140.5	n.685C>T		non_coding_transcript_exon_variant	1/16	2
P3H3	ENST00000544813.5	n.64-157C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60674 AN: 151740 Hom.: 16485 Cov.: 31

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.280 AC: 165837 AN: 592930 Hom.: 27250 Cov.: 8 AF XY: 0.282 AC XY: 89649 AN XY: 317856

Gnomad4 AFR exome AF: 0.778

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.504

Gnomad4 SAS exome AF: 0.345

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.400 AC: 60763 AN: 151858 Hom.: 16526 Cov.: 31 AF XY: 0.396 AC XY: 29371 AN XY: 74246

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.407

Alfa AF: 0.277 Hom.: 9301

Bravo AF: 0.426

Asia WGS AF: 0.406 AC: 1409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.85
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: rs3741920; hg19: chr12-6938872;