rs17040196

Variant names:

• chr3-14704350-G-A
• rs17040196
• NM_032137.5:c.892G>A

Variant summary

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

The NM_032137.5(C3orf20):​c.892G>A​(p.Ala298Thr) 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 1,613,286 control chromosomes in the GnomAD database, including 135,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 (12938 hom., cov: 31)
  • Exomes 𝑓: 0.41 (122773 hom.)
• Consequence: C3orf20 NM_032137.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 22 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=1.2806058E-4).
• 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.892G>A	p.Ala298Thr	missense	Exon 7 of 17	NP_115513.4
	C3orf20	NM_001184957.2		c.526G>A	p.Ala176Thr	missense	Exon 7 of 17	NP_001171886.1
	C3orf20	NM_001184958.2		c.526G>A	p.Ala176Thr	missense	Exon 7 of 17	NP_001171887.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3orf20	ENST00000253697.8	TSL:1 MANE Select	c.892G>A	p.Ala298Thr	missense	Exon 7 of 17	ENSP00000253697.3
	C3orf20	ENST00000412910.1	TSL:1	c.526G>A	p.Ala176Thr	missense	Exon 7 of 17	ENSP00000396081.1
	C3orf20	ENST00000435614.5	TSL:1	c.526G>A	p.Ala176Thr	missense	Exon 7 of 17	ENSP00000402933.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62156 AN: 151740 Hom.: 12924 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.434

GnomAD2 exomes AF: 0.394 AC: 98933 AN: 250808 AF XY: 0.389

Gnomad AFR exome AF: 0.430

Gnomad AMR exome AF: 0.444

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.337

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.411

Gnomad OTH exome AF: 0.418

GnomAD4 exome AF: 0.407 AC: 594718 AN: 1461428 Hom.: 122773 Cov.: 47 AF XY: 0.404 AC XY: 293643 AN XY: 727028

African (AFR) AF: 0.430 AC: 14403 AN: 33474

American (AMR) AF: 0.446 AC: 19930 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 13360 AN: 26134

East Asian (EAS) AF: 0.327 AC: 12998 AN: 39694

South Asian (SAS) AF: 0.317 AC: 27302 AN: 86246

European-Finnish (FIN) AF: 0.310 AC: 16525 AN: 53390

Middle Eastern (MID) AF: 0.473 AC: 2724 AN: 5764

European-Non Finnish (NFE) AF: 0.416 AC: 461930 AN: 1111626

Other (OTH) AF: 0.423 AC: 25546 AN: 60378

GnomAD4 genome AF: 0.410 AC: 62203 AN: 151858 Hom.: 12938 Cov.: 31 AF XY: 0.403 AC XY: 29897 AN XY: 74224

African (AFR) AF: 0.431 AC: 17833 AN: 41416

American (AMR) AF: 0.440 AC: 6711 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1782 AN: 3468

East Asian (EAS) AF: 0.336 AC: 1726 AN: 5134

South Asian (SAS) AF: 0.307 AC: 1480 AN: 4814

European-Finnish (FIN) AF: 0.299 AC: 3156 AN: 10544

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28171 AN: 67902

Other (OTH) AF: 0.436 AC: 920 AN: 2112

Alfa AF: 0.421 Hom.: 29108

Bravo AF: 0.424

TwinsUK AF: 0.414 AC: 1535

ALSPAC AF: 0.415 AC: 1599

ESP6500AA AF: 0.431 AC: 1898

ESP6500EA AF: 0.425 AC: 3657

ExAC AF: 0.392 AC: 47597

Asia WGS AF: 0.339 AC: 1177 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	0.088
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.13
DANN	Benign	0.42
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.00013	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.33
PROVEAN	Benign	0.35	N
REVEL	Benign	0.028
Sift	Benign	0.43	T
Sift4G	Benign	0.32	T
Polyphen		0.017	B
Vest4		0.014
MPC		0.087
ClinPred		0.0010	T
GERP RS		-3.0
Varity_R		0.020
gMVP		0.18
Mutation Taster		=100/0	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: rs17040196; hg19: chr3-14745857; COSMIC: COSV53783121; COSMIC: COSV53783121;