chr3-48446877-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_130384.3(ATRIP):c.32G>C(p.Arg11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,401,080 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11K) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ATRIP
NM_130384.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.672

Publications

1 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 links:

ATRIP-TREX1 (HGNC:):

ATRIP-TREX1 links:

CCDC51 (HGNC:25714): (coiled-coil domain containing 51) Enables mitochondrial ATP-gated potassium channel activity. Involved in potassium ion transmembrane transport. Is integral component of mitochondrial inner membrane. Part of mitochondrial ATP-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

CCDC51 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20153016).

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.32G>C	p.Arg11Thr	missense	Exon 1 of 13	NP_569055.1	Q8WXE1-1
ATRIP	NM_032166.4		c.32G>C	p.Arg11Thr	missense	Exon 1 of 12	NP_115542.2
ATRIP	NM_001271022.2		c.-218+78G>C		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.32G>C	p.Arg11Thr	missense	Exon 1 of 13	ENSP00000323099.3	Q8WXE1-1
ATRIP	ENST00000346691.9	TSL:1	c.32G>C	p.Arg11Thr	missense	Exon 1 of 12	ENSP00000302338.5	Q8WXE1-2
ATRIP	ENST00000949799.1		c.32G>C	p.Arg11Thr	missense	Exon 1 of 14	ENSP00000619858.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000103

AC:

AN:

97038

AF XY:

0.0000181

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1249038

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

610750

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25180

American (AMR)

AF:

0.00

AC:

AN:

17296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16680

East Asian (EAS)

AF:

0.00

AC:

AN:

30830

South Asian (SAS)

AF:

0.0000205

AC:

AN:

48876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43864

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3616

European-Non Finnish (NFE)

AF:

0.0000109

AC:

AN:

1012370

Other (OTH)

AF:

0.0000199

AC:

AN:

50326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000132

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67968

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000180

AC:

ClinVar

ClinVar submissions

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

Benign

0.23

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.048

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.81

M_CAP

Benign

0.069

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

0.67

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.61

REVEL

Benign

0.031

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.017

Polyphen

0.56

Vest4

0.40

MutPred

0.26

Gain of phosphorylation at R11 (P = 5e-04)

MVP

0.31

MPC

1.1

ClinPred

0.37

GERP RS

-0.14

PromoterAI

-0.17

Neutral

(source)

Varity_R

0.087

gMVP

0.35

Mutation Taster

=95/5

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