rs150432961

Variant names:

• chr5-132198270-T-A
• rs150432961
• NM_001365677.2:c.1307A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-132198270-T-A
• chr5-132198270-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365677.2(P4HA2):​c.1307A>T​(p.Asn436Ile) variant causes a missense, splice region 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. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: P4HA2 NM_001365677.2 missense, splice_region
• Scores: Splicing: ADA: 0.00003003
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

Genes affected

P4HA2 (HGNC:8547): (prolyl 4-hydroxylase subunit alpha 2) 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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23045129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P4HA2	NM_001365677.2	c.1307A>T	p.Asn436Ile	missense_variant, splice_region_variant	Exon 12 of 15	ENST00000379104.7	NP_001352606.1
P4HA2	NM_001017974.2	c.1365+51A>T		intron_variant	Intron 12 of 14	ENST00000360568.8	NP_001017974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P4HA2	ENST00000379104.7	c.1307A>T	p.Asn436Ile	missense_variant, splice_region_variant	Exon 12 of 15	1	NM_001365677.2	ENSP00000368398.2
P4HA2	ENST00000360568.8	c.1365+51A>T		intron_variant	Intron 12 of 14	1	NM_001017974.2	ENSP00000353772.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	.;.;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.5	N;N;N
REVEL	Benign	0.039
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.0050	B;B;B
Vest4		0.43
MutPred		0.47		Loss of disorder (P = 0.026);Loss of disorder (P = 0.026);Loss of disorder (P = 0.026);
MVP		0.60
MPC		0.30
ClinPred		0.43	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000030
dbscSNV1_RF	Benign	0.054
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

Publications

LitVar

Other links and lift over

dbSNP: rs150432961; hg19: chr5-131533963;