dbSNP rs559200861: PAXIP1:p.Pro688Pro (chr7-154962384-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_007349.4(PAXIP1):c.2064G>A(p.Pro688Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,612,752 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

PAXIP1
NM_007349.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.965

Publications

1 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 7-154962384-C-T is Benign according to our data. Variant chr7-154962384-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3414592.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.965 with no splicing effect.

BS2

High AC in GnomAd4 at 6 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAXIP1	NM_007349.4	MANE Select	c.2064G>A	p.Pro688Pro	synonymous	Exon 10 of 21	NP_031375.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAXIP1	ENST00000404141.6	TSL:5 MANE Select	c.2064G>A	p.Pro688Pro	synonymous	Exon 10 of 21	ENSP00000384048.1	Q6ZW49-6
PAXIP1	ENST00000919354.1		c.1842G>A	p.Pro614Pro	synonymous	Exon 7 of 18	ENSP00000589413.1
PAXIP1	ENST00000457196.5	TSL:5	n.*1783G>A		non_coding_transcript_exon	Exon 11 of 22	ENSP00000392011.1	F8WC23

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151352

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000631

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000963

AC:

AN:

249272

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461282

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726928

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.000179

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26112

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.000580

AC:

AN:

86182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111610

Other (OTH)

AF:

0.0000497

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000396

AC:

AN:

151470

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41256

American (AMR)

AF:

0.0000657

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000195

AC:

AN:

5116

South Asian (SAS)

AF:

0.000631

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67788

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000282

Hom.:

Bravo

AF:

0.0000189

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.6

(source)

DANN

Benign

0.60

PhyloP100

-0.96

Mutation Taster

=99/1

polymorphism

(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