10-73045029-T-C

Variant names:

• chr10-73045029-T-C
• NM_001017962.3:c.1100A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001017962.3(P4HA1):​c.1100A>G​(p.Asn367Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: P4HA1 NM_001017962.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.65
• Publications: 0 publications found

Genes affected

P4HA1 (HGNC:8546): (prolyl 4-hydroxylase subunit alpha 1) This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
P4HA1	NM_001017962.3	c.1100A>G	p.Asn367Ser	missense_variant	Exon 9 of 15	ENST00000394890.7	NP_001017962.1
P4HA1	NM_001142595.2	c.1100A>G	p.Asn367Ser	missense_variant	Exon 10 of 16		NP_001136067.1
P4HA1	NM_000917.4	c.1078-1072A>G		intron_variant	Intron 8 of 14		NP_000908.2
P4HA1	NM_001142596.2	c.1078-1072A>G		intron_variant	Intron 8 of 13		NP_001136068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P4HA1	ENST00000394890.7	c.1100A>G	p.Asn367Ser	missense_variant	Exon 9 of 15	1	NM_001017962.3	ENSP00000378353.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1100A>G (p.N367S) alteration is located in exon 10 (coding exon 8) of the P4HA1 gene. This alteration results from a A to G substitution at nucleotide position 1100, causing the asparagine (N) at amino acid position 367 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D;D
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	.;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M;M
PhyloP100		7.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.031	D;D
Polyphen		0.0040	B;B
Vest4		0.79
MutPred		0.26		Gain of phosphorylation at N367 (P = 0.0618);Gain of phosphorylation at N367 (P = 0.0618);
MVP		0.56
ClinPred		0.88	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

hg19: chr10-74804787;