NM_014262.5:c.499-151C>T

Variant names:

• chr12-6829708-C-T
• rs3741920
• NM_014262.5:c.499-151C>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.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
• Publications: 25 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]

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

Our verdict: Benign. The variant received -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.

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.499-151C>T		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.499-151C>T		intron	N/A	ENSP00000478600.1	Q8IVL6-1
	P3H3	ENST00000913254.1		c.499-151C>T		intron	N/A	ENSP00000583313.1
	P3H3	ENST00000942946.1		c.499-151C>T		intron	N/A	ENSP00000613005.1

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

African (AFR) AF: 0.778 AC: 11473 AN: 14754

American (AMR) AF: 0.229 AC: 5213 AN: 22716

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 6512 AN: 17990

East Asian (EAS) AF: 0.504 AC: 16623 AN: 32978

South Asian (SAS) AF: 0.345 AC: 20571 AN: 59636

European-Finnish (FIN) AF: 0.169 AC: 6023 AN: 35690

Middle Eastern (MID) AF: 0.435 AC: 1085 AN: 2494

European-Non Finnish (NFE) AF: 0.236 AC: 88418 AN: 375348

Other (OTH) AF: 0.317 AC: 9919 AN: 31324

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

African (AFR) AF: 0.767 AC: 31794 AN: 41428

American (AMR) AF: 0.295 AC: 4500 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1254 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2357 AN: 5130

South Asian (SAS) AF: 0.352 AC: 1696 AN: 4818

European-Finnish (FIN) AF: 0.168 AC: 1779 AN: 10560

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.235 AC: 15983 AN: 67872

Other (OTH) AF: 0.407 AC: 859 AN: 2112

Alfa AF: 0.307 Hom.: 23032

Bravo AF: 0.426

Asia WGS AF: 0.406 AC: 1409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3741920; hg19: chr12-6938872;