rs3135946

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_130384.3(ATRIP):c.*2083T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00778 in 1,595,078 control chromosomes in the GnomAD database, including 620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 314 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 306 hom. )

Consequence

ATRIP
NM_130384.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.999

Publications

7 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:

TREX1 (HGNC:12269): (three prime repair exonuclease 1) This gene encodes a nuclear protein with 3' exonuclease activity. The encoded protein may play a role in DNA repair and serve as a proofreading function for DNA polymerase. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, Cree encephalitis, and other diseases of the immune system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

TREX1 links:

ATRIP-TREX1 (HGNC:):

ATRIP-TREX1 links:

SHISA5 (HGNC:30376): (shisa family member 5) This gene encodes a member of the shisa family. The encoded protein is localized to the endoplasmic reticulum, and together with p53 induces apoptosis in a caspase-dependent manner. Alternative splicing results in multiple transcript variants. Related pseudogenes of this gene are found on chromosome X. [provided by RefSeq, Apr 2016]

SHISA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 3-48467637-T-C is Benign according to our data. Variant chr3-48467637-T-C is described in ClinVar as Benign. ClinVar VariationId is 345780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ATRIP	NM_130384.3 link	c.*2083T>C	3_prime_UTR_variant	Exon 13 of 13	ENST00000320211.10	NP_569055.1
TREX1	NM_033629.6 link	c.*37T>C	3_prime_UTR_variant	Exon 2 of 2	ENST00000625293.3	NP_338599.1
SHISA5	NM_016479.6 link	c.*1470A>G	downstream_gene_variant		ENST00000296444.7	NP_057563.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ATRIP	ENST00000320211.10 link	c.*2083T>C	3_prime_UTR_variant	Exon 13 of 13	1	NM_130384.3	ENSP00000323099.3
TREX1	ENST00000625293.3 link	c.*37T>C	3_prime_UTR_variant	Exon 2 of 2	6	NM_033629.6	ENSP00000486676.2
SHISA5	ENST00000296444.7 link	c.*1470A>G	downstream_gene_variant		1	NM_016479.6	ENSP00000296444.2

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5470

AN:

152166

Hom.:

306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.0277

GnomAD2 exomes

AF:

0.0104

AC:

2368

AN:

226624

AF XY:

0.00832

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.00805

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000497

Gnomad NFE exome

AF:

0.00136

Gnomad OTH exome

AF:

0.00888

GnomAD4 exome

AF:

0.00478

AC:

6902

AN:

1442794

Hom.:

306

Cov.:

AF XY:

0.00442

AC XY:

3167

AN XY:

715932

show subpopulations

African (AFR)

AF:

0.128

AC:

4237

AN:

33142

American (AMR)

AF:

0.00934

AC:

408

AN:

43660

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

408

AN:

24410

East Asian (EAS)

AF:

0.00

AC:

AN:

39566

South Asian (SAS)

AF:

0.000411

AC:

AN:

82778

European-Finnish (FIN)

AF:

0.0000586

AC:

AN:

51234

Middle Eastern (MID)

AF:

0.0169

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.000938

AC:

1034

AN:

1102692

Other (OTH)

AF:

0.0114

AC:

682

AN:

59648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

347

694

1040

1387

1734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.0362

AC:

5512

AN:

152284

Hom.:

314

Cov.:

AF XY:

0.0358

AC XY:

2665

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.121

AC:

5032

AN:

41542

American (AMR)

AF:

0.0156

AC:

238

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00160

AC:

109

AN:

68016

Other (OTH)

AF:

0.0274

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

241

481

722

962

1203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0264

Hom.:

Bravo

AF:

0.0415

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 07, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aicardi Goutieres syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.87

(source)

DANN

Benign

0.33

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over