3-50559661-G-C

Position:

• chr3-50559661-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016210.5(C3orf18):​c.485C>G​(p.Ala162Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000035 in 1,429,182 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A162V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000035 (0 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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3orf18	NM_016210.5	c.485C>G	p.Ala162Gly	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>G	p.Ala162Gly	missense_variant	6/6	1	NM_016210.5	ENSP00000349732	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000995 AC: 2 AN: 201088 Hom.: 0 AF XY: 0.00000925 AC XY: 1 AN XY: 108114

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000232

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000350 AC: 5 AN: 1429182 Hom.: 0 Cov.: 46 AF XY: 0.00000141 AC XY: 1 AN XY: 707542

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000457

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T;T;.;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	.;.;D;D;D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.47	T;T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	2.0	M;M;M;.;.
MutationTaster	Benign	0.0000078	P;P;P;P;P
PROVEAN	Benign	-0.59	N;N;N;N;N
REVEL	Benign	0.20
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		0.45
MutPred		0.37		Gain of catalytic residue at A162 (P = 0.0591);Gain of catalytic residue at A162 (P = 0.0591);Gain of catalytic residue at A162 (P = 0.0591);.;.;
MVP		0.48
MPC		0.57
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.41
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;