chr12-6838864-T-G

Variant names:

• chr12-6838864-T-G
• rs4963516
• NM_014262.5:c.1906-136T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014262.5(P3H3):​c.1906-136T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 648,778 control chromosomes in the GnomAD database, including 8,443 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 0.15 (1871 hom., cov: 32)
  • Exomes 𝑓: 0.15 (6572 hom.)
• Consequence: P3H3 NM_014262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 15 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 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.1906-136T>G		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.1906-136T>G		intron	N/A	ENSP00000478600.1	Q8IVL6-1
	P3H3	ENST00000612048.4	TSL:1	n.1439-136T>G		intron	N/A
	P3H3	ENST00000913254.1		c.1936-136T>G		intron	N/A	ENSP00000583313.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22970 AN: 152032 Hom.: 1867 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.150 AC: 74552 AN: 496628 Hom.: 6572 AF XY: 0.149 AC XY: 37170 AN XY: 249518

African (AFR) AF: 0.125 AC: 1556 AN: 12496

American (AMR) AF: 0.294 AC: 3389 AN: 11540

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 575 AN: 11420

East Asian (EAS) AF: 0.316 AC: 8252 AN: 26150

South Asian (SAS) AF: 0.126 AC: 2301 AN: 18260

European-Finnish (FIN) AF: 0.177 AC: 4568 AN: 25870

Middle Eastern (MID) AF: 0.0528 AC: 147 AN: 2786

European-Non Finnish (NFE) AF: 0.139 AC: 50228 AN: 362514

Other (OTH) AF: 0.138 AC: 3536 AN: 25592

GnomAD4 genome AF: 0.151 AC: 22985 AN: 152150 Hom.: 1871 Cov.: 32 AF XY: 0.156 AC XY: 11567 AN XY: 74384

African (AFR) AF: 0.131 AC: 5424 AN: 41518

American (AMR) AF: 0.227 AC: 3469 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 184 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1454 AN: 5178

South Asian (SAS) AF: 0.157 AC: 758 AN: 4820

European-Finnish (FIN) AF: 0.181 AC: 1917 AN: 10594

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9396 AN: 67976

Other (OTH) AF: 0.121 AC: 255 AN: 2102

Alfa AF: 0.136 Hom.: 2397

Bravo AF: 0.157

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.6
DANN	Benign	0.81
PhyloP100		-1.6
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: rs4963516; hg19: chr12-6948028; COSMIC: COSV51834901; COSMIC: COSV51834901;