3-14703199-G-A

Position:

• chr3-14703199-G-A

Variant summary

Our verdict is Likely benign. Variant got -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. 14/20 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

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058855087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C3orf20	NM_032137.5	c.815G>A	p.Ser272Asn	missense_variant	6/17	ENST00000253697.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3orf20	ENST00000253697.8	c.815G>A	p.Ser272Asn	missense_variant	6/17	1	NM_032137.5	P2
C3orf20	ENST00000412910.1	c.449G>A	p.Ser150Asn	missense_variant	6/17	1		A2
C3orf20	ENST00000435614.5	c.449G>A	p.Ser150Asn	missense_variant	6/17	1		A2

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

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.815G>A (p.S272N) alteration is located in exon 6 (coding exon 4) of the C3orf20 gene. This alteration results from a G to A substitution at nucleotide position 815, causing the serine (S) at amino acid position 272 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.26	N;.;.
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.34	N;N;N
REVEL	Benign	0.048
Sift	Benign	0.46	T;T;T
Sift4G	Benign	0.51	T;T;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-14744706;