3-14757381-C-G

Variant names:

• chr3-14757381-C-G
• rs745503373
• NM_032137.5:c.1951C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032137.5(C3orf20):​c.1951C>G​(p.Arg651Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. R651C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C3orf20 NM_032137.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34
• Publications: 0 publications found

Genes affected

C3orf20 (HGNC:25320): (chromosome 3 open reading frame 20) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C3orf20 Gene-Disease associations (from GenCC):

• neuromyelitis optica

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061214447).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032137.5. 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
	C3orf20	NM_032137.5	MANE Select	c.1951C>G	p.Arg651Gly	missense	Exon 13 of 17	NP_115513.4
	C3orf20	NM_001184957.2		c.1585C>G	p.Arg529Gly	missense	Exon 13 of 17	NP_001171886.1	Q8ND61-2
	C3orf20	NM_001184958.2		c.1585C>G	p.Arg529Gly	missense	Exon 13 of 17	NP_001171887.1	Q8ND61-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3orf20	ENST00000253697.8	TSL:1 MANE Select	c.1951C>G	p.Arg651Gly	missense	Exon 13 of 17	ENSP00000253697.3	Q8ND61-1
	C3orf20	ENST00000412910.1	TSL:1	c.1585C>G	p.Arg529Gly	missense	Exon 13 of 17	ENSP00000396081.1	Q8ND61-2
	C3orf20	ENST00000435614.5	TSL:1	c.1585C>G	p.Arg529Gly	missense	Exon 13 of 17	ENSP00000402933.1	Q8ND61-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458598 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 725552

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111360

Other (OTH) AF: 0.00 AC: 0 AN: 60152

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.049
DANN	Benign	0.86
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		-3.3
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.068
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		0.0020	B
Vest4		0.079
MutPred		0.29		Loss of sheet (P = 0.0228)
MVP		0.014
MPC		0.11
ClinPred		0.23	T
GERP RS		-6.5
Varity_R		0.076
gMVP		0.25
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs745503373; hg19: chr3-14798888;