dbSNP rs1034405: C3orf18:p.Ala162Val (chr3-50559661-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_016210.5(C3orf18):c.485C>T(p.Ala162Val) variant causes a missense change. The variant allele was found at a frequency of 0.866 in 1,580,864 control chromosomes in the GnomAD database, including 594,529 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 0.82 ( 52003 hom., cov: 34)

Exomes 𝑓: 0.87 ( 542526 hom. )

Consequence

C3orf18
NM_016210.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.51

Publications

48 publications found

Variant links:

Genes affected

C3orf18 (HGNC:24837): (chromosome 3 open reading frame 18) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C3orf18 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=7.807378E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C3orf18	NM_016210.5 link	c.485C>T	p.Ala162Val	missense_variant	Exon 6 of 6	ENST00000357203.8	NP_057294.2	Q9UK00-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C3orf18	ENST00000357203.8 link	c.485C>T	p.Ala162Val	missense_variant	Exon 6 of 6	1	NM_016210.5	ENSP00000349732.3		Q9UK00-1

Frequencies

GnomAD3 genomes

AF:

0.821

AC:

124949

AN:

152144

Hom.:

51998

Cov.:

show subpopulations

Gnomad AFR

AF:

0.680

Gnomad AMI

AF:

0.879

Gnomad AMR

AF:

0.858

Gnomad ASJ

AF:

0.932

Gnomad EAS

AF:

0.934

Gnomad SAS

AF:

0.904

Gnomad FIN

AF:

0.876

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.868

Gnomad OTH

AF:

0.851

GnomAD2 exomes

AF:

0.876

AC:

176186

AN:

201088

AF XY:

0.880

show subpopulations

Gnomad AFR exome

AF:

0.678

Gnomad AMR exome

AF:

0.911

Gnomad ASJ exome

AF:

0.932

Gnomad EAS exome

AF:

0.931

Gnomad FIN exome

AF:

0.870

Gnomad NFE exome

AF:

0.866

Gnomad OTH exome

AF:

0.881

GnomAD4 exome

AF:

0.870

AC:

1243511

AN:

1428602

Hom.:

542526

Cov.:

AF XY:

0.872

AC XY:

616912

AN XY:

707242

show subpopulations

African (AFR)

AF:

0.669

AC:

22000

AN:

32868

American (AMR)

AF:

0.903

AC:

36504

AN:

40412

Ashkenazi Jewish (ASJ)

AF:

0.930

AC:

23647

AN:

25432

East Asian (EAS)

AF:

0.934

AC:

35661

AN:

38180

South Asian (SAS)

AF:

0.910

AC:

74059

AN:

81358

European-Finnish (FIN)

AF:

0.869

AC:

44489

AN:

51210

Middle Eastern (MID)

AF:

0.925

AC:

5279

AN:

5706

European-Non Finnish (NFE)

AF:

0.869

AC:

950722

AN:

1094396

Other (OTH)

AF:

0.866

AC:

51150

AN:

59040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

7790

15579

23369

31158

38948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21122

42244

63366

84488

105610

<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:

0.821

AC:

124996

AN:

152262

Hom.:

52003

Cov.:

AF XY:

0.824

AC XY:

61387

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.679

AC:

28202

AN:

41514

American (AMR)

AF:

0.859

AC:

13142

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.932

AC:

3235

AN:

3472

East Asian (EAS)

AF:

0.934

AC:

4844

AN:

5184

South Asian (SAS)

AF:

0.904

AC:

4361

AN:

4826

European-Finnish (FIN)

AF:

0.876

AC:

9301

AN:

10612

Middle Eastern (MID)

AF:

0.908

AC:

267

AN:

294

European-Non Finnish (NFE)

AF:

0.868

AC:

59049

AN:

68028

Other (OTH)

AF:

0.849

AC:

1795

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1149

2298

3446

4595

5744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.856

Hom.:

206196

Bravo

AF:

0.814

TwinsUK

AF:

0.868

AC:

3220

ALSPAC

AF:

0.873

AC:

3366

ESP6500AA

AF:

0.693

AC:

3043

ESP6500EA

AF:

0.871

AC:

7491

ExAC

AF:

0.853

AC:

101510

Asia WGS

AF:

0.881

AC:

3061

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

T;T;T;.;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

.;.;D;D;D

MetaRNN

Benign

7.8e-7

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;M;.;.

PhyloP100

6.5

PROVEAN

Benign

-0.58

N;N;N;N;N

REVEL

Benign

0.23

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;D;D;.;.

Vest4

0.38

MPC

0.57

ClinPred

0.025

GERP RS

5.1

Varity_R

0.40

gMVP

0.38

Mutation Taster

=98/2

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