3-50559661-G-A

Position:

• chr3-50559661-G-A

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
C3orf18	NM_016210.5	c.485C>T	p.Ala162Val	missense_variant	6/6	ENST00000357203.8	NP_057294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3orf18	ENST00000357203.8	c.485C>T	p.Ala162Val	missense_variant	6/6	1	NM_016210.5	ENSP00000349732	P1

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

GnomAD3 exomes AF: 0.876 AC: 176186 AN: 201088 Hom.: 77506 AF XY: 0.880 AC XY: 95125 AN XY: 108114

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 SAS exome AF: 0.914

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

Gnomad4 AFR exome AF: 0.669

Gnomad4 AMR exome AF: 0.903

Gnomad4 ASJ exome AF: 0.930

Gnomad4 EAS exome AF: 0.934

Gnomad4 SAS exome AF: 0.910

Gnomad4 FIN exome AF: 0.869

Gnomad4 NFE exome AF: 0.869

Gnomad4 OTH exome AF: 0.866

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

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.932

Gnomad4 EAS AF: 0.934

Gnomad4 SAS AF: 0.904

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.868

Gnomad4 OTH AF: 0.849

Alfa AF: 0.863 Hom.: 96154

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	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	28
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	D
LIST_S2	Uncertain	0.89	.;.;D;D;D
MetaRNN	Benign	7.8e-7	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M;M;.;.
MutationTaster	Benign	0.0000061	P;P;P;P;P
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	T
GERP RS		5.1
Varity_R		0.40
gMVP		0.38

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

LitVar

Other links and lift over

dbSNP: rs1034405; hg19: chr3-50597092;