rs765426315

Variant names:

• chr5-132203830-T-A
• NM_001365677.2:c.1169A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-132203830-T-A
• chr5-132203830-T-C

Variant summary

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

The NM_001017974.2(P4HA2):​c.1169A>T​(p.Asp390Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: P4HA2 NM_001017974.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15

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=0.14444384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P4HA2	NM_001365677.2	c.1169A>T	p.Asp390Val	missense_variant	Exon 10 of 15	ENST00000379104.7	NP_001352606.1
P4HA2	NM_001017974.2	c.1169A>T	p.Asp390Val	missense_variant	Exon 10 of 15	ENST00000360568.8	NP_001017974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P4HA2	ENST00000379104.7	c.1169A>T	p.Asp390Val	missense_variant	Exon 10 of 15	1	NM_001365677.2	ENSP00000368398.2
P4HA2	ENST00000360568.8	c.1169A>T	p.Asp390Val	missense_variant	Exon 10 of 15	1	NM_001017974.2	ENSP00000353772.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461234 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727000

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.25	T;.;T;.;.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	.;.;.;.;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;L;L;L;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N
REVEL	Benign	0.068
Sift	Benign	0.54	T;T;T;T;T;T
Sift4G	Benign	0.48	T;T;T;T;T;T
Polyphen		0.019	B;B;B;B;B;B
Vest4		0.47
MutPred		0.43		Loss of disorder (P = 0.0335);Loss of disorder (P = 0.0335);Loss of disorder (P = 0.0335);Loss of disorder (P = 0.0335);Loss of disorder (P = 0.0335);Loss of disorder (P = 0.0335);
MVP		0.62
MPC		0.35
ClinPred		0.35	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-131539523;