Genetic Variant RNASE3:p.Thr124Arg (chr14-20892057-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002935.3(RNASE3):c.371C>G(p.Thr124Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,611,768 control chromosomes in the GnomAD database, including 420,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 34417 hom., cov: 30)

Exomes 𝑓: 0.72 ( 385906 hom. )

Consequence

RNASE3
NM_002935.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.14

Publications

46 publications found

Variant links:

Genes affected

RNASE3 (HGNC:10046): (ribonuclease A family member 3) The protein encoded by this gene belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein exhibits antimicrobial activity against pathogenic bacteria [provided by RefSeq, Oct 2014]

RNASE3 links:

ENSG00000259130 (HGNC:):

ENSG00000259130 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE3	NM_002935.3 link	c.371C>G	p.Thr124Arg	missense_variant	Exon 2 of 2	ENST00000304639.4	NP_002926.2	P12724
LOC100507513	XR_110261.4 link	n.723-16314G>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASE3	ENST00000304639.4 link	c.371C>G	p.Thr124Arg	missense_variant	Exon 2 of 2	1	NM_002935.3	ENSP00000302324.3		P12724

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

98433

AN:

150342

Hom.:

34395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.773

Gnomad ASJ

AF:

0.717

Gnomad EAS

AF:

0.732

Gnomad SAS

AF:

0.693

Gnomad FIN

AF:

0.799

Gnomad MID

AF:

0.707

Gnomad NFE

AF:

0.732

Gnomad OTH

AF:

0.676

GnomAD2 exomes

AF:

0.725

AC:

182236

AN:

251208

AF XY:

0.724

show subpopulations

Gnomad AFR exome

AF:

0.413

Gnomad AMR exome

AF:

0.857

Gnomad ASJ exome

AF:

0.714

Gnomad EAS exome

AF:

0.721

Gnomad FIN exome

AF:

0.804

Gnomad NFE exome

AF:

0.726

Gnomad OTH exome

AF:

0.731

GnomAD4 exome

AF:

0.724

AC:

1057712

AN:

1461306

Hom.:

385906

Cov.:

AF XY:

0.723

AC XY:

525724

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.411

AC:

13663

AN:

33226

American (AMR)

AF:

0.847

AC:

37897

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.715

AC:

18686

AN:

26132

East Asian (EAS)

AF:

0.742

AC:

29456

AN:

39698

South Asian (SAS)

AF:

0.687

AC:

59233

AN:

86246

European-Finnish (FIN)

AF:

0.801

AC:

42798

AN:

53418

Middle Eastern (MID)

AF:

0.689

AC:

3971

AN:

5764

European-Non Finnish (NFE)

AF:

0.728

AC:

808911

AN:

1111724

Other (OTH)

AF:

0.714

AC:

43097

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

17874

35748

53622

71496

89370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19978

39956

59934

79912

99890

<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:

0.655

AC:

98489

AN:

150462

Hom.:

34417

Cov.:

AF XY:

0.658

AC XY:

48398

AN XY:

73550

show subpopulations

African (AFR)

AF:

0.418

AC:

16736

AN:

40000

American (AMR)

AF:

0.773

AC:

11756

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.717

AC:

2489

AN:

3470

East Asian (EAS)

AF:

0.732

AC:

3769

AN:

5146

South Asian (SAS)

AF:

0.694

AC:

3329

AN:

4796

European-Finnish (FIN)

AF:

0.799

AC:

8460

AN:

10584

Middle Eastern (MID)

AF:

0.716

AC:

209

AN:

292

European-Non Finnish (NFE)

AF:

0.732

AC:

49719

AN:

67956

Other (OTH)

AF:

0.677

AC:

1421

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1493

2986

4479

5972

7465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.712

Hom.:

27292

Bravo

AF:

0.640

TwinsUK

AF:

0.718

AC:

2663

ALSPAC

AF:

0.726

AC:

2798

ESP6500AA

AF:

0.442

AC:

1936

ESP6500EA

AF:

0.717

AC:

6170

ExAC

AF:

0.715

AC:

86695

Asia WGS

AF:

0.703

AC:

2445

AN:

3478

EpiCase

AF:

0.712

EpiControl

AF:

0.709

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.035

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.063

Eigen

Benign

-2.7

Eigen_PC

Benign

-2.6

FATHMM_MKL

Benign

0.00027

LIST_S2

Benign

0.11

MetaRNN

Benign

0.0000042

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.9

PhyloP100

-3.1

PrimateAI

Benign

0.24

PROVEAN

Benign

3.9

REVEL

Benign

0.057

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.042

MPC

0.043

ClinPred

0.00087

GERP RS

-3.4

Varity_R

0.046

gMVP

0.79

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.31

Position offset: 1

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