3-50559661-G-T

Variant names:

• chr3-50559661-G-T
• rs1034405
• NM_016210.5:c.485C>A
• C3orf18 p.Ala162Glu

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.51
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016210.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3orf18	NM_016210.5	MANE Select	c.485C>A	p.Ala162Glu	missense	Exon 6 of 6	NP_057294.2	Q9UK00-1
	C3orf18	NM_001171740.3		c.485C>A	p.Ala162Glu	missense	Exon 5 of 5	NP_001165211.1	Q9UK00-1
	C3orf18	NM_001171741.3		c.485C>A	p.Ala162Glu	missense	Exon 5 of 5	NP_001165212.1	Q9UK00-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3orf18	ENST00000357203.8	TSL:1 MANE Select	c.485C>A	p.Ala162Glu	missense	Exon 6 of 6	ENSP00000349732.3	Q9UK00-1
	C3orf18	ENST00000426034.5	TSL:1	c.485C>A	p.Ala162Glu	missense	Exon 5 of 5	ENSP00000387606.1	Q9UK00-1
	C3orf18	ENST00000449241.5	TSL:1	c.485C>A	p.Ala162Glu	missense	Exon 5 of 5	ENSP00000404913.1	Q9UK00-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1429182 Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0 AN XY: 707542

African (AFR) AF: 0.00 AC: 0 AN: 32906

American (AMR) AF: 0.00 AC: 0 AN: 40458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25438

East Asian (EAS) AF: 0.00 AC: 0 AN: 38190

South Asian (SAS) AF: 0.00 AC: 0 AN: 81420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094766

Other (OTH) AF: 0.00 AC: 0 AN: 59062

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.5
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.55
gMVP		0.47
Mutation Taster		=87/13	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1034405;

hg19: chr3-50597092;