11-74283240-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182904.5(P4HA3):c.1110+2569T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 152,166 control chromosomes in the GnomAD database, including 507 homozygotes. 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: 𝑓 0.051 (507 hom., cov: 32)
• Consequence: P4HA3 NM_182904.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

Genes affected

P4HA3 (HGNC:30135): (prolyl 4-hydroxylase subunit alpha 3) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P4HA3	NM_182904.5	c.1110+2569T>A		intron_variant		ENST00000331597.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HA3	ENST00000331597.9	c.1110+2569T>A		intron_variant		1	NM_182904.5	P1
P4HA3	ENST00000524388.5	c.*512+2569T>A		intron_variant, NMD_transcript_variant		1
P4HA3	ENST00000525968.1	c.*761+2569T>A		intron_variant, NMD_transcript_variant		1
P4HA3	ENST00000427714.2	c.1110+2569T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0507 AC: 7716 AN: 152048 Hom.: 507 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0508 AC: 7733 AN: 152166 Hom.: 507 Cov.: 32 AF XY: 0.0490 AC XY: 3648 AN XY: 74404

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0242

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.00671 Hom.: 1

Bravo AF: 0.0547

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.6
Dann	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs10488771; hg19: chr11-73994285;