dbSNP rs17040196: C3orf20:p.Ala298Thr (chr3-14704350-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032137.5(C3orf20):c.892G>A(p.Ala298Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,613,286 control chromosomes in the GnomAD database, including 135,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.41 ( 12938 hom., cov: 31)

Exomes 𝑓: 0.41 ( 122773 hom. )

Consequence

C3orf20
NM_032137.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.327

Publications

22 publications found

Variant links:

Genes affected

C3orf20 (HGNC:25320): (chromosome 3 open reading frame 20) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C3orf20 Gene-Disease associations (from GenCC):

neuromyelitis optica
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

C3orf20 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2806058E-4).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C3orf20	NM_032137.5 link	c.892G>A	p.Ala298Thr	missense_variant	Exon 7 of 17	ENST00000253697.8	NP_115513.4	Q8ND61-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C3orf20	ENST00000253697.8 link	c.892G>A	p.Ala298Thr	missense_variant	Exon 7 of 17	1	NM_032137.5	ENSP00000253697.3	Q8ND61-1
C3orf20	ENST00000412910.1 link	c.526G>A	p.Ala176Thr	missense_variant	Exon 7 of 17	1		ENSP00000396081.1	Q8ND61-2
C3orf20	ENST00000435614.5 link	c.526G>A	p.Ala176Thr	missense_variant	Exon 7 of 17	1		ENSP00000402933.1	Q8ND61-2
C3orf20	ENST00000495387.1 link	n.-5G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

62156

AN:

151740

Hom.:

12924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.514

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.415

Gnomad OTH

AF:

0.434

GnomAD2 exomes

AF:

0.394

AC:

98933

AN:

250808

AF XY:

0.389

show subpopulations

Gnomad AFR exome

AF:

0.430

Gnomad AMR exome

AF:

0.444

Gnomad ASJ exome

AF:

0.510

Gnomad EAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.418

GnomAD4 exome

AF:

0.407

AC:

594718

AN:

1461428

Hom.:

122773

Cov.:

AF XY:

0.404

AC XY:

293643

AN XY:

727028

show subpopulations

African (AFR)

AF:

0.430

AC:

14403

AN:

33474

American (AMR)

AF:

0.446

AC:

19930

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

13360

AN:

26134

East Asian (EAS)

AF:

0.327

AC:

12998

AN:

39694

South Asian (SAS)

AF:

0.317

AC:

27302

AN:

86246

European-Finnish (FIN)

AF:

0.310

AC:

16525

AN:

53390

Middle Eastern (MID)

AF:

0.473

AC:

2724

AN:

5764

European-Non Finnish (NFE)

AF:

0.416

AC:

461930

AN:

1111626

Other (OTH)

AF:

0.423

AC:

25546

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

18787

37575

56362

75150

93937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14254

28508

42762

57016

71270

<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:

0.410

AC:

62203

AN:

151858

Hom.:

12938

Cov.:

AF XY:

0.403

AC XY:

29897

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.431

AC:

17833

AN:

41416

American (AMR)

AF:

0.440

AC:

6711

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

1782

AN:

3468

East Asian (EAS)

AF:

0.336

AC:

1726

AN:

5134

South Asian (SAS)

AF:

0.307

AC:

1480

AN:

4814

European-Finnish (FIN)

AF:

0.299

AC:

3156

AN:

10544

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.415

AC:

28171

AN:

67902

Other (OTH)

AF:

0.436

AC:

920

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1832

3663

5495

7326

9158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.421

Hom.:

29108

Bravo

AF:

0.424

TwinsUK

AF:

0.414

AC:

1535

ALSPAC

AF:

0.415

AC:

1599

ESP6500AA

AF:

0.431

AC:

1898

ESP6500EA

AF:

0.425

AC:

3657

ExAC

AF:

0.392

AC:

47597

Asia WGS

AF:

0.339

AC:

1177

AN:

3478

EpiCase

AF:

0.425

EpiControl

AF:

0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.13

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.0034

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0079

LIST_S2

Benign

0.59

T;.;T

MetaRNN

Benign

0.00013

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

L;.;.

PhyloP100

-0.33

PROVEAN

Benign

0.35

N;N;N

REVEL

Benign

0.028

Sift

Benign

0.43

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.017

B;.;.

Vest4

0.014

MPC

0.087

ClinPred

0.0010

GERP RS

-3.0

Varity_R

0.020

gMVP

0.18

Mutation Taster

=100/0

polymorphism (auto)

(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

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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