3-14757403-G-A

Position:

• chr3-14757403-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032137.5(C3orf20):​c.1973G>A​(p.Arg658Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C3orf20 NM_032137.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.962

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11589697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C3orf20	NM_032137.5	c.1973G>A	p.Arg658Lys	missense_variant	13/17	ENST00000253697.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3orf20	ENST00000253697.8	c.1973G>A	p.Arg658Lys	missense_variant	13/17	1	NM_032137.5	P2
C3orf20	ENST00000412910.1	c.1607G>A	p.Arg536Lys	missense_variant	13/17	1		A2
C3orf20	ENST00000435614.5	c.1607G>A	p.Arg536Lys	missense_variant	13/17	1		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459504 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726058

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

phenotyping only

GenomeConnect-Association for Creatine Deficiencies, Association for Creatine Deficiencies

-

Variant interpreted as Uncertain significance and reported on 06-09-2017 by GTR ID 1006. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect facilitates ClinVar submission from the Association for Creatine Deficiencies registry and does not attempt to reinterpret the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.016	T;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.55	T;.;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.;.
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.91	N;N;N
REVEL	Benign	0.049
Sift	Benign	0.067	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.66	P;P;P
Vest4		0.27
MutPred		0.30		Gain of ubiquitination at R658 (P = 0.0128);.;.;
MVP		0.055
MPC		0.25
ClinPred		0.20	T
GERP RS		1.5
Varity_R		0.12
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1575157919; hg19: chr3-14798910;