rs3759348

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014262.5(P3H3):​c.1906-432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,906 control chromosomes in the GnomAD database, including 6,594 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 0.29 ( 6594 hom., cov: 32)

Consequence

P3H3
NM_014262.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

Publications

10 publications found
Variant links:
Genes affected
P3H3 (HGNC:19318): (prolyl 3-hydroxylase 3) The protein encoded by this gene belongs to the leprecan family of proteoglycans, which function as collagen prolyl hydroxylases that are required for proper collagen biosynthesis, folding and assembly. This protein, like other family members, is thought to reside in the endoplasmic reticulum. Epigenetic inactivation of this gene is associated with breast and other cancers, suggesting that it may function as a tumor suppressor. [provided by RefSeq, Aug 2013]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
P3H3NM_014262.5 linkc.1906-432C>T intron_variant Intron 13 of 14 ENST00000290510.10 NP_055077.2 Q8IVL6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
P3H3ENST00000290510.10 linkc.1906-432C>T intron_variant Intron 13 of 14 1 NM_014262.5 ENSP00000478600.1 Q8IVL6-1
P3H3ENST00000612048.4 linkn.1439-432C>T intron_variant Intron 12 of 13 1
P3H3ENST00000536140.5 linkn.2536-432C>T intron_variant Intron 14 of 15 2

Frequencies

GnomAD3 genomes
AF:
0.291
AC:
44176
AN:
151788
Hom.:
6592
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.260
Gnomad AMI
AF:
0.185
Gnomad AMR
AF:
0.324
Gnomad ASJ
AF:
0.349
Gnomad EAS
AF:
0.372
Gnomad SAS
AF:
0.333
Gnomad FIN
AF:
0.277
Gnomad MID
AF:
0.348
Gnomad NFE
AF:
0.293
Gnomad OTH
AF:
0.315
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.291
AC:
44188
AN:
151906
Hom.:
6594
Cov.:
32
AF XY:
0.291
AC XY:
21567
AN XY:
74216
show subpopulations
African (AFR)
AF:
0.259
AC:
10719
AN:
41398
American (AMR)
AF:
0.324
AC:
4944
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
0.349
AC:
1210
AN:
3468
East Asian (EAS)
AF:
0.371
AC:
1919
AN:
5170
South Asian (SAS)
AF:
0.332
AC:
1594
AN:
4800
European-Finnish (FIN)
AF:
0.277
AC:
2925
AN:
10552
Middle Eastern (MID)
AF:
0.354
AC:
104
AN:
294
European-Non Finnish (NFE)
AF:
0.293
AC:
19927
AN:
67938
Other (OTH)
AF:
0.320
AC:
677
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1585
3171
4756
6342
7927
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
456
912
1368
1824
2280
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.294
Hom.:
7821
Bravo
AF:
0.292
Asia WGS
AF:
0.336
AC:
1166
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.90
DANN
Benign
0.72
PhyloP100
-1.3
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs3759348; hg19: chr12-6947732; API