Genetic Variant ENST00000612048.4:n.1811A>G (chr12-6839528-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000612048.4(P3H3):n.1811A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 1,506,996 control chromosomes in the GnomAD database, including 336,065 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 0.68 ( 35269 hom., cov: 31)

Exomes 𝑓: 0.66 ( 300796 hom. )

Consequence

P3H3
ENST00000612048.4 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0270

Publications

28 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]

P3H3 links:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H3	NM_014262.5 link	c.*67A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000290510.10	NP_055077.2	Q8IVL6-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
P3H3	ENST00000612048.4 link	n.1811A>G	non_coding_transcript_exon_variant	Exon 14 of 14	1
P3H3	ENST00000290510.10 link	c.*67A>G	3_prime_UTR_variant	Exon 15 of 15	1	NM_014262.5	ENSP00000478600.1	Q8IVL6-1
P3H3	ENST00000536140.5 link	n.2908A>G	non_coding_transcript_exon_variant	Exon 16 of 16	2

Frequencies

GnomAD3 genomes

AF:

0.676

AC:

102688

AN:

151848

Hom.:

35238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.716

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.738

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.976

Gnomad SAS

AF:

0.807

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.666

GnomAD4 exome

AF:

0.662

AC:

896556

AN:

1355030

Hom.:

300796

Cov.:

AF XY:

0.665

AC XY:

442851

AN XY:

665694

show subpopulations

African (AFR)

AF:

0.718

AC:

21933

AN:

30532

American (AMR)

AF:

0.787

AC:

25814

AN:

32806

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

13140

AN:

23210

East Asian (EAS)

AF:

0.986

AC:

34876

AN:

35372

South Asian (SAS)

AF:

0.799

AC:

60133

AN:

75264

European-Finnish (FIN)

AF:

0.571

AC:

24541

AN:

43002

Middle Eastern (MID)

AF:

0.626

AC:

2479

AN:

3960

European-Non Finnish (NFE)

AF:

0.641

AC:

675822

AN:

1054808

Other (OTH)

AF:

0.674

AC:

37818

AN:

56076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

15082

30164

45245

60327

75409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18430

36860

55290

73720

92150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.676

AC:

102768

AN:

151966

Hom.:

35269

Cov.:

AF XY:

0.680

AC XY:

50475

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.716

AC:

29636

AN:

41418

American (AMR)

AF:

0.739

AC:

11290

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

1988

AN:

3472

East Asian (EAS)

AF:

0.976

AC:

5044

AN:

5166

South Asian (SAS)

AF:

0.807

AC:

3883

AN:

4814

European-Finnish (FIN)

AF:

0.573

AC:

6053

AN:

10562

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.628

AC:

42664

AN:

67938

Other (OTH)

AF:

0.670

AC:

1413

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1653

3306

4960

6613

8266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.640

Hom.:

31193

Bravo

AF:

0.692

Asia WGS

AF:

0.870

AC:

3021

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.6

(source)

DANN

Benign

0.36

PhyloP100

-0.027

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over