Genetic Variant NM_007349.4:c.1542T>C (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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007349.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAXIP1	NM_007349.4	MANE Select	c.1542T>C	p.Leu514Leu	synonymous	Exon 7 of 21	NP_031375.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PAXIP1	ENST00000404141.6	TSL:5 MANE Select	c.1542T>C	p.Leu514Leu	synonymous	Exon 7 of 21	ENSP00000384048.1
PAXIP1	ENST00000457196.5	TSL:5	n.*1261T>C		non_coding_transcript_exon	Exon 8 of 22	ENSP00000392011.1
PAXIP1	ENST00000473219.5	TSL:5	n.3482T>C		non_coding_transcript_exon	Exon 7 of 21

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over