rs1034405

Variant names:

• chr3-50559661-G-A
• rs1034405
• NM_016210.5:c.485C>T
• C3orf18 p.Ala162Val

Your query was ambiguous. Multiple possible variants found:

• chr3-50559661-G-A
• chr3-50559661-G-C
• chr3-50559661-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.51
• Publications: 48 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: 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.

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>T	p.Ala162Val	missense	Exon 6 of 6	NP_057294.2	Q9UK00-1
	C3orf18	NM_001171740.3		c.485C>T	p.Ala162Val	missense	Exon 5 of 5	NP_001165211.1	Q9UK00-1
	C3orf18	NM_001171741.3		c.485C>T	p.Ala162Val	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>T	p.Ala162Val	missense	Exon 6 of 6	ENSP00000349732.3	Q9UK00-1
	C3orf18	ENST00000426034.5	TSL:1	c.485C>T	p.Ala162Val	missense	Exon 5 of 5	ENSP00000387606.1	Q9UK00-1
	C3orf18	ENST00000449241.5	TSL:1	c.485C>T	p.Ala162Val	missense	Exon 5 of 5	ENSP00000404913.1	Q9UK00-1

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124949 AN: 152144 Hom.: 51998 Cov.: 34

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

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.: 46 AF XY: 0.872 AC XY: 616912 AN XY: 707242

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

GnomAD4 genome AF: 0.821 AC: 124996 AN: 152262 Hom.: 52003 Cov.: 34 AF XY: 0.824 AC XY: 61387 AN XY: 74474

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

Alfa AF: 0.856 Hom.: 206196

Bravo AF: 0.814

Asia WGS AF: 0.881 AC: 3061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	7.8e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.5
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.40
gMVP		0.38
Mutation Taster		=98/2	polymorphism (auto)

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;

COSMIC: COSV107454759;