1-40515059-G-T

Variant names:

Variant summary

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

The NM_001346953.2(EXO5):c.515G>T(p.Gly172Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,613,684 control chromosomes in the GnomAD database, including 132,479 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G172R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.47 ( 18211 hom., cov: 31)

Exomes 𝑓: 0.39 ( 114268 hom. )

Consequence

EXO5
NM_001346953.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.14

Publications

37 publications found

Variant links:

Genes affected

EXO5 (HGNC:26115): (exonuclease 5) The protein encoded by this gene is a single-stranded DNA (ssDNA)-specific exonuclease that can slide along the DNA before cutting it. However, human replication protein A binds ssDNA and restricts sliding of the encoded protein, providing a 5'-directionality to the enzyme. This protein localizes to nuclear repair loci after DNA damage. [provided by RefSeq, Nov 2016]

EXO5 links:

ENSG00000227278 (HGNC:):

ENSG00000227278 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 (MetaRNN=7.4286504E-6).

BP6

Variant 1-40515059-G-T is Benign according to our data. Variant chr1-40515059-G-T is described in ClinVar as Benign. ClinVar VariationId is 1252459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXO5	NM_001346953.2 link	c.515G>T	p.Gly172Val	missense_variant	Exon 4 of 4	ENST00000415550.6	NP_001333882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXO5	ENST00000415550.6 link	c.515G>T	p.Gly172Val	missense_variant	Exon 4 of 4	2	NM_001346953.2	ENSP00000413565.2

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71490

AN:

151802

Hom.:

18177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.551

Gnomad AMR

AF:

0.524

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.466

GnomAD2 exomes

AF:

0.445

AC:

111916

AN:

251346

AF XY:

0.439

show subpopulations

Gnomad AFR exome

AF:

0.654

Gnomad AMR exome

AF:

0.579

Gnomad ASJ exome

AF:

0.467

Gnomad EAS exome

AF:

0.489

Gnomad FIN exome

AF:

0.348

Gnomad NFE exome

AF:

0.363

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.387

AC:

565933

AN:

1461764

Hom.:

114268

Cov.:

AF XY:

0.390

AC XY:

283754

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.659

AC:

22069

AN:

33480

American (AMR)

AF:

0.570

AC:

25481

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.464

AC:

12121

AN:

26134

East Asian (EAS)

AF:

0.526

AC:

20879

AN:

39698

South Asian (SAS)

AF:

0.527

AC:

45431

AN:

86252

European-Finnish (FIN)

AF:

0.347

AC:

18502

AN:

53396

Middle Eastern (MID)

AF:

0.521

AC:

3004

AN:

5764

European-Non Finnish (NFE)

AF:

0.354

AC:

393099

AN:

1111922

Other (OTH)

AF:

0.420

AC:

25347

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

20490

40979

61469

81958

102448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12796

25592

38388

51184

63980

<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:

0.471

AC:

71574

AN:

151920

Hom.:

18211

Cov.:

AF XY:

0.473

AC XY:

35101

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.649

AC:

26886

AN:

41398

American (AMR)

AF:

0.524

AC:

8004

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

1606

AN:

3466

East Asian (EAS)

AF:

0.495

AC:

2556

AN:

5162

South Asian (SAS)

AF:

0.534

AC:

2572

AN:

4812

European-Finnish (FIN)

AF:

0.348

AC:

3680

AN:

10568

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.363

AC:

24647

AN:

67936

Other (OTH)

AF:

0.464

AC:

979

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1796

3593

5389

7186

8982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.403

Hom.:

63591

Bravo

AF:

0.491

TwinsUK

AF:

0.360

AC:

1334

ALSPAC

AF:

0.344

AC:

1325

ESP6500AA

AF:

0.638

AC:

2811

ESP6500EA

AF:

0.372

AC:

3196

ExAC

AF:

0.444

AC:

53925

Asia WGS

AF:

0.545

AC:

1898

AN:

3478

EpiCase

AF:

0.373

EpiControl

AF:

0.375

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 10, 2018

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.037

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0016

T;T;.;T;.;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.22

.;.;T;T;T;.;T

MetaRNN

Benign

0.0000074

T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-3.0

N;N;.;N;.;.;.

PhyloP100

2.1

PrimateAI

Benign

0.39

PROVEAN

Benign

4.2

N;N;N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

1.0

T;T;T;T;T;T;T

Sift4G

Benign

0.59

T;T;T;T;T;T;T

Polyphen

0.0

B;B;.;B;.;.;.

Vest4

0.071

MPC

0.18

ClinPred

0.0034

GERP RS

4.0

Varity_R

0.092

gMVP

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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