3-58869477-A-T

Variant names:

• chr3-58869477-A-T
• rs757759275
• NM_001394063.1:c.866T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001351532.2(CFAP20DC):​c.-65T>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CFAP20DC NM_001351532.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12584653).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351532.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP20DC	NM_001394063.1	MANE Select	c.866T>A	p.Val289Asp	missense	Exon 9 of 17	NP_001380992.1	A0A2U3TZK7
	CFAP20DC	NM_001351532.2		c.-65T>A		5_prime_UTR_premature_start_codon_gain	Exon 9 of 15	NP_001338461.1
	CFAP20DC	NM_001351530.2		c.701T>A	p.Val234Asp	missense	Exon 8 of 16	NP_001338459.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP20DC	ENST00000482387.7	TSL:5 MANE Select	c.866T>A	p.Val289Asp	missense	Exon 9 of 17	ENSP00000417122.2	A0A2U3TZK7
	CFAP20DC	ENST00000468415.6	TSL:1	n.*296T>A		non_coding_transcript_exon	Exon 9 of 15	ENSP00000419142.2	F8WF72
	CFAP20DC	ENST00000468415.6	TSL:1	n.*296T>A		3_prime_UTR	Exon 9 of 15	ENSP00000419142.2	F8WF72

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457714 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725054

African (AFR) AF: 0.00 AC: 0 AN: 33344

American (AMR) AF: 0.00 AC: 0 AN: 44018

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25990

East Asian (EAS) AF: 0.00 AC: 0 AN: 39554

South Asian (SAS) AF: 0.00 AC: 0 AN: 85140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110360

Other (OTH) AF: 0.0000166 AC: 1 AN: 60210

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Uncertain	0.98
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.62
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.028
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.57	P
Vest4		0.27
MutPred		0.26		Gain of glycosylation at S83 (P = 0.0141)
MVP		0.33
MPC		0.50
ClinPred		0.79	D
GERP RS		1.5
gMVP		0.45
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs757759275; hg19: chr3-58855203;