3-14703199-G-A

Variant names:

• chr3-14703199-G-A
• NM_032137.5:c.815G>A

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.815G>A​(p.Ser272Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C3orf20 NM_032137.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.51
• 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=0.058855087).

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.815G>A	p.Ser272Asn	missense	Exon 6 of 17	NP_115513.4
	C3orf20	NM_001184957.2		c.449G>A	p.Ser150Asn	missense	Exon 6 of 17	NP_001171886.1	Q8ND61-2
	C3orf20	NM_001184958.2		c.449G>A	p.Ser150Asn	missense	Exon 6 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.815G>A	p.Ser272Asn	missense	Exon 6 of 17	ENSP00000253697.3	Q8ND61-1
	C3orf20	ENST00000412910.1	TSL:1	c.449G>A	p.Ser150Asn	missense	Exon 6 of 17	ENSP00000396081.1	Q8ND61-2
	C3orf20	ENST00000435614.5	TSL:1	c.449G>A	p.Ser150Asn	missense	Exon 6 of 17	ENSP00000402933.1	Q8ND61-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727226

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.041
DANN	Benign	0.73
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.26	N
PhyloP100		-1.5
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.048
Sift	Benign	0.46	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.075		Loss of phosphorylation at S272 (P = 0.0477)
MVP		0.055
MPC		0.076
ClinPred		0.041	T
GERP RS		-10
Varity_R		0.037
gMVP		0.082
Mutation Taster		=99/1	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

hg19: chr3-14744706;