rs545796791

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_130384.3(ATRIP):c.93C>G(p.Ser31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000258 in 1,472,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S31N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ATRIP
NM_130384.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.530

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.050603896).

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.93C>G	p.Ser31Arg	missense	Exon 1 of 13	NP_569055.1	Q8WXE1-1
ATRIP	NM_032166.4		c.93C>G	p.Ser31Arg	missense	Exon 1 of 12	NP_115542.2
ATRIP	NM_001271022.2		c.-218+139C>G		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.93C>G	p.Ser31Arg	missense	Exon 1 of 13	ENSP00000323099.3	Q8WXE1-1
ATRIP	ENST00000346691.9	TSL:1	c.93C>G	p.Ser31Arg	missense	Exon 1 of 12	ENSP00000302338.5	Q8WXE1-2
ATRIP	ENST00000949799.1		c.93C>G	p.Ser31Arg	missense	Exon 1 of 14	ENSP00000619858.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000785

AC:

AN:

127390

AF XY:

0.0000947

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00106

Gnomad EAS exome

AF:

0.000162

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000242

AC:

AN:

1320286

Hom.:

Cov.:

AF XY:

0.0000322

AC XY:

AN XY:

652600

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26974

American (AMR)

AF:

0.00

AC:

AN:

23282

Ashkenazi Jewish (ASJ)

AF:

0.000935

AC:

AN:

21384

East Asian (EAS)

AF:

0.00

AC:

AN:

30660

South Asian (SAS)

AF:

0.0000892

AC:

AN:

67284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47644

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4918

European-Non Finnish (NFE)

AF:

0.00000191

AC:

AN:

1044410

Other (OTH)

AF:

0.0000744

AC:

AN:

53730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.0000394

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41560

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.0000712

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000697

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Benign

0.038

Eigen_PC

Benign

0.057

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.72

M_CAP

Benign

0.046

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

0.53

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.9

REVEL

Benign

0.051

Sift

Benign

0.035

Sift4G

Benign

0.16

Polyphen

0.077

Vest4

0.36

MutPred

0.27

Loss of glycosylation at S31 (P = 0.0086)

MVP

0.38

MPC

0.45

ClinPred

0.074

GERP RS

3.5

PromoterAI

-0.014

Neutral

(source)

Varity_R

0.19

gMVP

0.27

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over