Genetic Variant NM_023015.5:c.2835G>C (chr1-153772652-G-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_023015.5(INTS3):c.2835G>C(p.Thr945Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 1,613,996 control chromosomes in the GnomAD database, including 9,293 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 3278 hom., cov: 32)

Exomes 𝑓: 0.071 ( 6015 hom. )

Consequence

INTS3
NM_023015.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.795

Publications

16 publications found

Variant links:

Genes affected

INTS3 (HGNC:26153): (integrator complex subunit 3) The protein encoded by this gene can form a complex with human single-strand DNA binding proteins 1 or 2 (hSSB1 and hSSB2) and other proteins to mediate genome stability and the DNA damage response. The encoded protein is also part of a multiprotein complex that interacts with the C-terminal domain of RNA polymerase II large subunit to help regulate processing of U1 and U2 small nuclear RNAs. [provided by RefSeq, May 2016]

INTS3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP7

Synonymous conserved (PhyloP=-0.795 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS3	NM_023015.5 link	c.2835G>C	p.Thr945Thr	synonymous_variant	Exon 28 of 30	ENST00000318967.7	NP_075391.3	Q68E01-2
INTS3	NM_001324475.2 link	c.2835G>C	p.Thr945Thr	synonymous_variant	Exon 29 of 31		NP_001311404.1	Q68E01-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS3	ENST00000318967.7 link	c.2835G>C	p.Thr945Thr	synonymous_variant	Exon 28 of 30	1	NM_023015.5	ENSP00000318641.2		Q68E01-2

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

23020

AN:

152038

Hom.:

3258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0855

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.00674

Gnomad SAS

AF:

0.0826

Gnomad FIN

AF:

0.0431

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.0634

Gnomad OTH

AF:

0.135

GnomAD2 exomes

AF:

0.0845

AC:

21229

AN:

251370

AF XY:

0.0809

show subpopulations

Gnomad AFR exome

AF:

0.390

Gnomad AMR exome

AF:

0.0563

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.00527

Gnomad FIN exome

AF:

0.0410

Gnomad NFE exome

AF:

0.0661

Gnomad OTH exome

AF:

0.0859

GnomAD4 exome

AF:

0.0710

AC:

103765

AN:

1461840

Hom.:

6015

Cov.:

AF XY:

0.0709

AC XY:

51541

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.397

AC:

13291

AN:

33480

American (AMR)

AF:

0.0587

AC:

2627

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

3382

AN:

26136

East Asian (EAS)

AF:

0.00418

AC:

166

AN:

39698

South Asian (SAS)

AF:

0.0871

AC:

7514

AN:

86252

European-Finnish (FIN)

AF:

0.0396

AC:

2114

AN:

53408

Middle Eastern (MID)

AF:

0.220

AC:

1269

AN:

5768

European-Non Finnish (NFE)

AF:

0.0612

AC:

68021

AN:

1111978

Other (OTH)

AF:

0.0891

AC:

5381

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

5395

10791

16186

21582

26977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2718

5436

8154

10872

13590

<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:

0.152

AC:

23089

AN:

152156

Hom.:

3278

Cov.:

AF XY:

0.149

AC XY:

11095

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.379

AC:

15728

AN:

41462

American (AMR)

AF:

0.0852

AC:

1303

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

508

AN:

3470

East Asian (EAS)

AF:

0.00676

AC:

AN:

5180

South Asian (SAS)

AF:

0.0819

AC:

395

AN:

4824

European-Finnish (FIN)

AF:

0.0431

AC:

457

AN:

10608

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0634

AC:

4312

AN:

68008

Other (OTH)

AF:

0.134

AC:

283

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

844

1689

2533

3378

4222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.0615

Hom.:

163

Bravo

AF:

0.164

Asia WGS

AF:

0.0650

AC:

226

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

6.3

(source)

DANN

Benign

0.75

PhyloP100

-0.80

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Computational scores

Splicing

Publications

Other links and lift over