Variant 7-154968480-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007349.4(PAXIP1):c.1721C>T(p.Pro574Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000037 in 1,217,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

PAXIP1
NM_007349.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.538

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:

PAXIP1 (HGNC:):

PAXIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006186396).

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAXIP1	NM_007349.4 linkuse as main transcript	c.1721C>T	p.Pro574Leu	missense_variant	7/21	ENST00000404141.6	NP_031375.3	Q6ZW49-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAXIP1	ENST00000404141.6 linkuse as main transcript	c.1721C>T	p.Pro574Leu	missense_variant	7/21	5	NM_007349.4	ENSP00000384048.1		Q6ZW49-6

Frequencies

GnomAD3 genomes

AF:

0.0000467

AC:

AN:

149852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000998

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000140

AC:

AN:

157526

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

83102

show subpopulations

Gnomad AFR exome

AF:

0.000122

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00180

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1067884

Hom.:

Cov.:

AF XY:

0.0000333

AC XY:

AN XY:

540672

show subpopulations

Gnomad4 AFR exome

AF:

0.0000795

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000562

Gnomad4 SAS exome

AF:

0.0000138

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000167

Gnomad4 OTH exome

AF:

0.0000638

GnomAD4 genome

AF:

0.0000467

AC:

AN:

149852

Hom.:

Cov.:

AF XY:

0.0000410

AC XY:

AN XY:

73136

show subpopulations

Gnomad4 AFR

AF:

0.0000246

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000998

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.0000189

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.1721C>T (p.P574L) alteration is located in exon 7 (coding exon 7) of the PAXIP1 gene. This alteration results from a C to T substitution at nucleotide position 1721, causing the proline (P) at amino acid position 574 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.57

DANN

Benign

0.59

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.59

.;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.020

Sift

Benign

0.24

T;T

Sift4G

Benign

0.076

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.29

Loss of glycosylation at P574 (P = 0.0018);Loss of glycosylation at P574 (P = 0.0018);

MVP

0.13

MPC

0.15

ClinPred

0.0049

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.014

gMVP

0.073

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over