rs17040196

chr3-14704350-G-A

Variant summary

Our verdict is Benign. Variant got -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. 12/18 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C3orf20	NM_032137.5	c.892G>A	p.Ala298Thr	missense_variant	7/17	ENST00000253697.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3orf20	ENST00000253697.8	c.892G>A	p.Ala298Thr	missense_variant	7/17	1	NM_032137.5	P2
C3orf20	ENST00000412910.1	c.526G>A	p.Ala176Thr	missense_variant	7/17	1		A2
C3orf20	ENST00000435614.5	c.526G>A	p.Ala176Thr	missense_variant	7/17	1		A2
C3orf20	ENST00000495387.1			upstream_gene_variant		3

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

GnomAD3 exomes AF: 0.394 AC: 98933 AN: 250808 Hom.: 20094 AF XY: 0.389 AC XY: 52789 AN XY: 135626

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 SAS exome AF: 0.312

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

Gnomad4 AFR exome AF: 0.430

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.511

Gnomad4 EAS exome AF: 0.327

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.423

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

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.436

Alfa AF: 0.423 Hom.: 20801

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 v4.3

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;.;T
MetaRNN	Benign	0.00013	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L;.;.
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	0.35	N;N;N
REVEL	Benign	0.028
Sift	Benign	0.43	T;T;T
Sift4G	Benign	0.32	T;T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs17040196; hg19: chr3-14745857; COSMIC: COSV53783121; COSMIC: COSV53783121;