chr3-14714110-C-G

Position:

• chr3-14714110-C-G

Variant summary

Our verdict is Benign. Variant got -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. 11/19 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 (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

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=0.0017674863).
• 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.1264C>G	p.Leu422Val	missense_variant	8/17	ENST00000253697.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3orf20	ENST00000253697.8	c.1264C>G	p.Leu422Val	missense_variant	8/17	1	NM_032137.5	P2
C3orf20	ENST00000412910.1	c.898C>G	p.Leu300Val	missense_variant	8/17	1		A2
C3orf20	ENST00000435614.5	c.898C>G	p.Leu300Val	missense_variant	8/17	1		A2
C3orf20	ENST00000495387.1	n.368C>G		non_coding_transcript_exon_variant	2/5	3

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

GnomAD3 exomes AF: 0.395 AC: 99073 AN: 250910 Hom.: 20143 AF XY: 0.390 AC XY: 52826 AN XY: 135598

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 SAS exome AF: 0.313

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

Gnomad4 AFR exome AF: 0.430

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.512

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.423

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

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.433

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 v4.3

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;.;T
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M;.;.
MutationTaster	Benign	0.92	P;P;P
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.061
Sift	Benign	0.15	T;T;T
Sift4G	Pathogenic	0.0	D;D;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

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