Genetic Variant NM_007349.4:c.2836A>C (chr7-154947989-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007349.4(PAXIP1):c.2836A>C(p.Ile946Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I946V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PAXIP1
NM_007349.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.259

Publications

0 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:

PAXIP1-AS2 (HGNC:48958): (PAXIP1 antisense RNA 2)

PAXIP1-AS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08712557).

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.2836A>C	p.Ile946Leu	missense	Exon 17 of 21	NP_031375.3
	PAXIP1-AS2	NR_024476.1		n.1420T>G		non_coding_transcript_exon	Exon 7 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAXIP1	ENST00000404141.6	TSL:5 MANE Select	c.2836A>C	p.Ile946Leu	missense	Exon 17 of 21	ENSP00000384048.1	Q6ZW49-6
PAXIP1	ENST00000919354.1		c.2614A>C	p.Ile872Leu	missense	Exon 14 of 18	ENSP00000589413.1
PAXIP1-AS2	ENST00000449486.1	TSL:2	n.1409T>G		non_coding_transcript_exon	Exon 7 of 8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110096

Other (OTH)

AF:

0.00

AC:

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.042

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.76

M_CAP

Benign

0.029

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.21

PhyloP100

0.26

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.11

REVEL

Benign

0.14

Sift

Benign

0.36

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.16

MutPred

0.48

Loss of catalytic residue at I946 (P = 0.003)

MVP

0.35

MPC

0.82

ClinPred

0.085

GERP RS

-1.8

Varity_R

0.11

gMVP

0.32

Mutation Taster

=93/7

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over