Genetic Variant PAXIP1:p.Leu514Leu (chr7-154968659-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007349.4(PAXIP1):c.1542T>C(p.Leu514Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 716,086 control chromosomes in the GnomAD database, including 129,922 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 0.59 ( 26538 hom., cov: 31)

Exomes 𝑓: 0.60 ( 103384 hom. )

Consequence

PAXIP1
NM_007349.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.460

Publications

15 publications found

Variant links:

Genes affected

PAXIP1 (HGNC:8624): (PAX interacting protein 1) This gene is a member of the paired box (PAX) gene family and encodes a nuclear protein with six BRCT (breast cancer carboxy-terminal) domains. This protein plays a critical role in maintaining genome stability, condensation of chromatin and progression through mitosis. [provided by RefSeq, Jul 2008]

PAXIP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP7

Synonymous conserved (PhyloP=-0.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAXIP1	NM_007349.4 link	c.1542T>C	p.Leu514Leu	synonymous_variant	Exon 7 of 21	ENST00000404141.6	NP_031375.3	Q6ZW49-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAXIP1	ENST00000404141.6 link	c.1542T>C	p.Leu514Leu	synonymous_variant	Exon 7 of 21	5	NM_007349.4	ENSP00000384048.1		Q6ZW49-6

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

89513

AN:

151140

Hom.:

26508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.544

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.667

Gnomad ASJ

AF:

0.640

Gnomad EAS

AF:

0.594

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.651

Gnomad MID

AF:

0.651

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.615

GnomAD2 exomes

AF:

0.624

AC:

96270

AN:

154284

AF XY:

0.619

show subpopulations

Gnomad AFR exome

AF:

0.535

Gnomad AMR exome

AF:

0.747

Gnomad ASJ exome

AF:

0.647

Gnomad EAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.644

Gnomad NFE exome

AF:

0.589

Gnomad OTH exome

AF:

0.631

GnomAD4 exome

AF:

0.603

AC:

340652

AN:

564828

Hom.:

103384

Cov.:

AF XY:

0.601

AC XY:

183152

AN XY:

304776

show subpopulations

African (AFR)

AF:

0.537

AC:

8488

AN:

15796

American (AMR)

AF:

0.742

AC:

25765

AN:

34716

Ashkenazi Jewish (ASJ)

AF:

0.642

AC:

12855

AN:

20020

East Asian (EAS)

AF:

0.563

AC:

18067

AN:

32102

South Asian (SAS)

AF:

0.608

AC:

38137

AN:

62730

European-Finnish (FIN)

AF:

0.646

AC:

31100

AN:

48152

Middle Eastern (MID)

AF:

0.634

AC:

2237

AN:

3526

European-Non Finnish (NFE)

AF:

0.584

AC:

185334

AN:

317154

Other (OTH)

AF:

0.609

AC:

18669

AN:

30632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

10198

20396

30595

40793

50991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.592

AC:

89596

AN:

151258

Hom.:

26538

Cov.:

AF XY:

0.597

AC XY:

44154

AN XY:

73904

show subpopulations

African (AFR)

AF:

0.544

AC:

22372

AN:

41110

American (AMR)

AF:

0.667

AC:

10176

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.640

AC:

2216

AN:

3462

East Asian (EAS)

AF:

0.593

AC:

3026

AN:

5106

South Asian (SAS)

AF:

0.624

AC:

2988

AN:

4786

European-Finnish (FIN)

AF:

0.651

AC:

6818

AN:

10474

Middle Eastern (MID)

AF:

0.651

AC:

190

AN:

292

European-Non Finnish (NFE)

AF:

0.589

AC:

39957

AN:

67782

Other (OTH)

AF:

0.612

AC:

1281

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1904

3808

5712

7616

9520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.590

Hom.:

4899

Bravo

AF:

0.593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.1

(source)

DANN

Benign

0.54

PhyloP100

-0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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