12-6838516-G-A

Position:

• chr12-6838516-G-A

Variant summary

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

The NM_014262.5(P3H3):​c.1905+483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,992 control chromosomes in the GnomAD database, including 6,533 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 (6533 hom., cov: 32)
• Consequence: P3H3 NM_014262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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/exons	MANE	UniProt
P3H3	NM_014262.5	c.1905+483G>A		intron_variant		ENST00000290510.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P3H3	ENST00000290510.10	c.1905+483G>A		intron_variant		1	NM_014262.5	P1
P3H3	ENST00000612048.4	n.1438+483G>A		intron_variant, non_coding_transcript_variant		1
P3H3	ENST00000536140.5	n.2535+483G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43991 AN: 151874 Hom.: 6530 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.290 AC: 44002 AN: 151992 Hom.: 6533 Cov.: 32 AF XY: 0.289 AC XY: 21496 AN XY: 74284

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.317

Alfa AF: 0.283 Hom.: 6653

Bravo AF: 0.291

Asia WGS AF: 0.333 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.82

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: rs3759347; hg19: chr12-6947680;