3-58863767-C-G

Position:

• chr3-58863767-C-G

Variant summary

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

The NM_001394063.1(CFAP20DC):​c.1384G>C​(p.Glu462Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 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)
• Consequence: CFAP20DC NM_001394063.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20

Genes affected

CFAP20DC (HGNC:24763): (CFAP20 domain containing)

CFAP20DC-AS1 (HGNC:41063): (CFAP20DC antisense RNA 1)

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=0.10812625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP20DC	NM_001394063.1	c.1384G>C	p.Glu462Gln	missense_variant	12/17	ENST00000482387.7	NP_001380992.1
CFAP20DC-AS1	NR_110820.1	n.105+39192C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP20DC	ENST00000482387.7	c.1384G>C	p.Glu462Gln	missense_variant	12/17	5	NM_001394063.1	ENSP00000417122	P1
CFAP20DC-AS1	ENST00000482372.1	n.105+39192C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Nov 12, 2021

The c.1009G>C (p.E337Q) alteration is located in exon 12 (coding exon 8) of the C3orf67 gene. This alteration results from a G to C substitution at nucleotide position 1009, causing the glutamic acid (E) at amino acid position 337 to be replaced by a glutamine (Q). 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
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Uncertain	0.99
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.78	T;D;D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;.
MutationTaster	Benign	0.57	D;D;N
PROVEAN	Benign	-0.27	N;.;N
REVEL	Benign	0.065
Sift	Benign	0.24	T;.;T
Sift4G	Benign	0.40	T;.;T
Polyphen		0.83	P;.;P
Vest4		0.10
MutPred		0.088		Loss of glycosylation at S333 (P = 0.1088);.;.;
MVP		0.22
MPC		0.45
ClinPred		0.63	D
GERP RS		4.5
gMVP		0.23

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: chr3-58849493;