NM_032137.5:c.1264C>G

Variant names:

• chr3-14714110-C-G
• rs6790129
• NM_032137.5:c.1264C>G

Variant summary

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

The NM_032137.5(C3orf20):​c.1264C>G​(p.Leu422Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,612,970 control chromosomes in the GnomAD database, including 135,891 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (12975 hom., cov: 32)
  • Exomes 𝑓: 0.41 (122916 hom.)
• Consequence: C3orf20 NM_032137.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 26 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017674863).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

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.1264C>G	p.Leu422Val	missense	Exon 8 of 17	NP_115513.4
	C3orf20	NM_001184957.2		c.898C>G	p.Leu300Val	missense	Exon 8 of 17	NP_001171886.1	Q8ND61-2
	C3orf20	NM_001184958.2		c.898C>G	p.Leu300Val	missense	Exon 8 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.1264C>G	p.Leu422Val	missense	Exon 8 of 17	ENSP00000253697.3	Q8ND61-1
	C3orf20	ENST00000412910.1	TSL:1	c.898C>G	p.Leu300Val	missense	Exon 8 of 17	ENSP00000396081.1	Q8ND61-2
	C3orf20	ENST00000435614.5	TSL:1	c.898C>G	p.Leu300Val	missense	Exon 8 of 17	ENSP00000402933.1	Q8ND61-2

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62254 AN: 151874 Hom.: 12961 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.432

GnomAD2 exomes AF: 0.395 AC: 99073 AN: 250910 AF XY: 0.390

Gnomad AFR exome AF: 0.430

Gnomad AMR exome AF: 0.444

Gnomad ASJ exome AF: 0.511

Gnomad EAS exome AF: 0.344

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.411

Gnomad OTH exome AF: 0.419

GnomAD4 exome AF: 0.407 AC: 594931 AN: 1460978 Hom.: 122916 Cov.: 43 AF XY: 0.404 AC XY: 293722 AN XY: 726800

African (AFR) AF: 0.430 AC: 14380 AN: 33448

American (AMR) AF: 0.446 AC: 19916 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 13366 AN: 26130

East Asian (EAS) AF: 0.334 AC: 13243 AN: 39676

South Asian (SAS) AF: 0.317 AC: 27330 AN: 86210

European-Finnish (FIN) AF: 0.309 AC: 16518 AN: 53376

Middle Eastern (MID) AF: 0.472 AC: 2679 AN: 5674

European-Non Finnish (NFE) AF: 0.416 AC: 461938 AN: 1111424

Other (OTH) AF: 0.423 AC: 25561 AN: 60368

GnomAD4 genome AF: 0.410 AC: 62302 AN: 151992 Hom.: 12975 Cov.: 32 AF XY: 0.403 AC XY: 29951 AN XY: 74300

African (AFR) AF: 0.430 AC: 17822 AN: 41424

American (AMR) AF: 0.440 AC: 6713 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3470

East Asian (EAS) AF: 0.346 AC: 1782 AN: 5154

South Asian (SAS) AF: 0.307 AC: 1476 AN: 4810

European-Finnish (FIN) AF: 0.299 AC: 3162 AN: 10576

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28219 AN: 67974

Other (OTH) AF: 0.433 AC: 915 AN: 2112

Alfa AF: 0.411 Hom.: 9441

Bravo AF: 0.424

TwinsUK AF: 0.414 AC: 1536

ALSPAC AF: 0.415 AC: 1599

ESP6500AA AF: 0.431 AC: 1899

ESP6500EA AF: 0.426 AC: 3660

ExAC AF: 0.393 AC: 47674

Asia WGS AF: 0.341 AC: 1185 AN: 3478

EpiCase AF: 0.425

EpiControl AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.012
Eigen_PC	Benign	-0.047
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.079
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.061
Sift	Benign	0.15	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.87	P
Vest4		0.076
MPC		0.31
ClinPred		0.068	T
GERP RS		1.6
Varity_R		0.086
gMVP		0.13
Mutation Taster		=97/3	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

Other links and lift over

dbSNP: rs6790129; hg19: chr3-14755617; COSMIC: COSV53783114;