1-42766891-C-T

Variant names:

• chr1-42766891-C-T
• rs201750444
• NM_022356.4:c.81G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001243246.2(P3H1):​c.81G>A​(p.Glu27Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: P3H1 NM_001243246.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 7 publications found

Genes affected

P3H1 (HGNC:19316): (prolyl 3-hydroxylase 1) This gene encodes an enzyme that is a member of the collagen prolyl hydroxylase family. These enzymes are localized to the endoplasmic reticulum and their activity is required for proper collagen synthesis and assembly. Mutations in this gene are associated with osteogenesis imperfecta type VIII. Three alternatively spliced transcript variants encoding different isoforms have been described. Other variants may exist, but their biological validity has not been determined. [provided by RefSeq, Aug 2011]

P3H1 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 8

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• osteogenesis imperfecta type 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=0.284 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243246.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H1	NM_022356.4	MANE Select	c.81G>A	p.Glu27Glu	synonymous	Exon 1 of 15	NP_071751.3
	P3H1	NM_001243246.2		c.81G>A	p.Glu27Glu	synonymous	Exon 1 of 14	NP_001230175.1
	P3H1	NM_001146289.2		c.81G>A	p.Glu27Glu	synonymous	Exon 1 of 15	NP_001139761.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H1	ENST00000296388.10	TSL:1 MANE Select	c.81G>A	p.Glu27Glu	synonymous	Exon 1 of 15	ENSP00000296388.5
	P3H1	ENST00000397054.7	TSL:1	c.81G>A	p.Glu27Glu	synonymous	Exon 1 of 15	ENSP00000380245.3
	P3H1	ENST00000492956.1	TSL:1	n.127G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 236666 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.94
PhyloP100		0.28
PromoterAI		0.023	Neutral
Mutation Taster		=100/0	polymorphism

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: rs201750444; hg19: chr1-43232562;