rs4963516

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-6838864-T-A
• chr12-6838864-T-C
• chr12-6838864-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014262.5(P3H3):​c.1906-136T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 497,302 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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>A		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>A		intron	N/A	ENSP00000478600.1	Q8IVL6-1
	P3H3	ENST00000612048.4	TSL:1	n.1439-136T>A		intron	N/A
	P3H3	ENST00000913254.1		c.1936-136T>A		intron	N/A	ENSP00000583313.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000201 AC: 1 AN: 497302 Hom.: 0 AF XY: 0.00000400 AC XY: 1 AN XY: 249872

African (AFR) AF: 0.00 AC: 0 AN: 12510

American (AMR) AF: 0.00 AC: 0 AN: 11566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11422

East Asian (EAS) AF: 0.00 AC: 0 AN: 26170

South Asian (SAS) AF: 0.00 AC: 0 AN: 18302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2786

European-Non Finnish (NFE) AF: 0.00000275 AC: 1 AN: 363034

Other (OTH) AF: 0.00 AC: 0 AN: 25616

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.5
DANN	Benign	0.85
PhyloP100		-1.6

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;