Genetic Variant C3orf18:p.Ala162Glu (chr3-50559661-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016210.5(C3orf18):c.485C>A(p.Ala162Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

C3orf18
NM_016210.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.51

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C3orf18	NM_016210.5 link	c.485C>A	p.Ala162Glu	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>A	p.Ala162Glu	missense_variant	Exon 6 of 6	1	NM_016210.5	ENSP00000349732.3		Q9UK00-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1429182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707542

African (AFR)

AF:

0.00

AC:

AN:

32906

American (AMR)

AF:

0.00

AC:

AN:

40458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25438

East Asian (EAS)

AF:

0.00

AC:

AN:

38190

South Asian (SAS)

AF:

0.00

AC:

AN:

81420

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094766

Other (OTH)

AF:

0.00

AC:

AN:

59062

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.069

T;T;T;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

.;.;T;T;T

M_CAP

Benign

0.073

MetaRNN

Uncertain

0.47

T;T;T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

2.0

M;M;M;.;.

PhyloP100

6.5

PROVEAN

Benign

-0.93

N;N;N;N;N

REVEL

Benign

0.21

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

MutPred

0.37

Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);.;.;

MVP

0.61

MPC

0.62

ClinPred

0.95

GERP RS

5.1

Varity_R

0.55

gMVP

0.47

Mutation Taster

=87/13

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over