rs5439

Positions:

• chr12-6839718-A-C
• chr12-6839718-A-G

Variant summary

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

The NM_014262.5(P3H3):​c.*257A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 492,052 control chromosomes in the GnomAD database, including 2,632 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 0.073 (604 hom., cov: 33)
  • Exomes 𝑓: 0.098 (2028 hom.)
• Consequence: P3H3 NM_014262.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P3H3	NM_014262.5	c.*257A>C		3_prime_UTR_variant	15/15	ENST00000290510.10	NP_055077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P3H3	ENST00000290510.10	c.*257A>C		3_prime_UTR_variant	15/15	1	NM_014262.5	ENSP00000478600.1
P3H3	ENST00000612048.4	n.2001A>C		non_coding_transcript_exon_variant	14/14	1
P3H3	ENST00000536140.5	n.3098A>C		non_coding_transcript_exon_variant	16/16	2

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11158 AN: 152178 Hom.: 601 Cov.: 33

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0729

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0918

Gnomad OTH AF: 0.0819

GnomAD4 exome AF: 0.0977 AC: 33179 AN: 339756 Hom.: 2028 Cov.: 3 AF XY: 0.102 AC XY: 17823 AN XY: 174776

Gnomad4 AFR exome AF: 0.0160

Gnomad4 AMR exome AF: 0.0640

Gnomad4 ASJ exome AF: 0.0948

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.0522

Gnomad4 NFE exome AF: 0.0895

Gnomad4 OTH exome AF: 0.0886

GnomAD4 genome AF: 0.0732 AC: 11155 AN: 152296 Hom.: 604 Cov.: 33 AF XY: 0.0748 AC XY: 5566 AN XY: 74454

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0729

Gnomad4 ASJ AF: 0.0983

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0918

Gnomad4 OTH AF: 0.0815

Alfa AF: 0.0879 Hom.: 568

Bravo AF: 0.0714

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.64
DANN	Benign	0.63

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: rs5439; hg19: chr12-6948882;