chr12-6837196-C-G

Variant names:

• chr12-6837196-C-G
• rs10849527
• NM_014262.5:c.1560+110C>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.1560+110C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000113 in 887,456 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: 0.0000011 (0 hom.)
• Consequence: P3H3 NM_014262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 6 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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H3	NM_014262.5	c.1560+110C>G		intron_variant	Intron 10 of 14	ENST00000290510.10	NP_055077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H3	ENST00000290510.10	c.1560+110C>G		intron_variant	Intron 10 of 14	1	NM_014262.5	ENSP00000478600.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000113 AC: 1 AN: 887456 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 449804

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20978

American (AMR) AF: 0.00 AC: 0 AN: 26888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18182

East Asian (EAS) AF: 0.00 AC: 0 AN: 33822

South Asian (SAS) AF: 0.00 AC: 0 AN: 62242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3266

European-Non Finnish (NFE) AF: 0.00000154 AC: 1 AN: 648852

Other (OTH) AF: 0.00 AC: 0 AN: 40892

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.061
DANN	Benign	0.66
PhyloP100		-2.4

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: rs10849527; hg19: chr12-6946360;