Genetic Variant NM_130384.3:c.65C>A (chr3-48446910-C-A) – 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_130384.3(ATRIP):c.65C>A(p.Pro22Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P22P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATRIP
NM_130384.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.981

Publications

0 publications found

Variant links:

Genes affected

ATRIP (HGNC:33499): (ATR interacting protein) This gene encodes an essential component of the DNA damage checkpoint. The encoded protein binds to single-stranded DNA coated with replication protein A. The protein also interacts with the ataxia telangiectasia and Rad3 related protein kinase, resulting in its accumulation at intranuclear foci induced by DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

ATRIP Gene-Disease associations (from GenCC):

breast cancer
Inheritance: AD Classification: MODERATE Submitted by: G2P
Seckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hereditary breast carcinoma
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ATRIP links:

ATRIP-TREX1 (HGNC:):

ATRIP-TREX1 links:

Genome browser will be placed here

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=0.09156492).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130384.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATRIP	NM_130384.3	MANE Select	c.65C>A	p.Pro22Gln	missense	Exon 1 of 13	NP_569055.1	Q8WXE1-1
ATRIP	NM_032166.4		c.65C>A	p.Pro22Gln	missense	Exon 1 of 12	NP_115542.2
ATRIP	NM_001271022.2		c.-218+111C>A		intron	N/A	NP_001257951.1	Q8WXE1-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATRIP	ENST00000320211.10	TSL:1 MANE Select	c.65C>A	p.Pro22Gln	missense	Exon 1 of 13	ENSP00000323099.3	Q8WXE1-1
ATRIP	ENST00000346691.9	TSL:1	c.65C>A	p.Pro22Gln	missense	Exon 1 of 12	ENSP00000302338.5	Q8WXE1-2
ATRIP	ENST00000949799.1		c.65C>A	p.Pro22Gln	missense	Exon 1 of 14	ENSP00000619858.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1240426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

605742

African (AFR)

AF:

0.00

AC:

AN:

25066

American (AMR)

AF:

0.00

AC:

AN:

12478

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17054

East Asian (EAS)

AF:

0.00

AC:

AN:

29722

South Asian (SAS)

AF:

0.00

AC:

AN:

51250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4068

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1007400

Other (OTH)

AF:

0.00

AC:

AN:

50290

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.046

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.75

M_CAP

Benign

0.037

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

0.98

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.97

REVEL

Benign

0.056

Sift

Benign

0.45

Sift4G

Benign

0.23

Polyphen

0.22

Vest4

0.38

MutPred

0.16

Loss of glycosylation at P22 (P = 0.0148)

MVP

0.32

MPC

0.77

ClinPred

0.20

GERP RS

1.6

PromoterAI

-0.048

Neutral

(source)

Varity_R

0.025

gMVP

0.17

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over