rs113593896

Variant names:

• chr1-42754892-T-A
• rs113593896
• NM_022356.4:c.1322A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-42754892-T-A
• chr1-42754892-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022356.4(P3H1):​c.1322A>T​(p.Asp441Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D441G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: P3H1 NM_022356.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H1	NM_022356.4	c.1322A>T	p.Asp441Val	missense_variant	Exon 8 of 15	ENST00000296388.10	NP_071751.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H1	ENST00000296388.10	c.1322A>T	p.Asp441Val	missense_variant	Exon 8 of 15	1	NM_022356.4	ENSP00000296388.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	.;.;T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.043	D;D;D
Polyphen		1.0, 0.98	.;D;D
Vest4		0.72
MutPred		0.24		Gain of methylation at K437 (P = 0.0506);Gain of methylation at K437 (P = 0.0506);Gain of methylation at K437 (P = 0.0506);
MVP		0.70
MPC		0.88
ClinPred		0.96	D
GERP RS		5.6
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.18
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs113593896; hg19: chr1-43220563;