3-58866572-G-C

Variant names:

• chr3-58866572-G-C
• rs139315615
• NM_001394063.1:c.1252C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001394063.1(CFAP20DC):​c.1252C>G​(p.Gln418Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,608,866 control chromosomes in the GnomAD database, including 21 homozygotes. 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (20 hom.)
• Consequence: CFAP20DC NM_001394063.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.23
• Publications: 6 publications found

Genes affected

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

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0064465106).
• BP6: Variant 3-58866572-G-C is Benign according to our data. Variant chr3-58866572-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 771135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 20 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394063.1. 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.1252C>G	p.Gln418Glu	missense	Exon 11 of 17	NP_001380992.1	A0A2U3TZK7
	CFAP20DC	NM_001351530.2		c.1087C>G	p.Gln363Glu	missense	Exon 10 of 16	NP_001338459.1
	CFAP20DC	NM_001351531.2		c.637C>G	p.Gln213Glu	missense	Exon 10 of 16	NP_001338460.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP20DC	ENST00000482387.7	TSL:5 MANE Select	c.1252C>G	p.Gln418Glu	missense	Exon 11 of 17	ENSP00000417122.2	A0A2U3TZK7
	CFAP20DC	ENST00000468415.6	TSL:1	n.*682C>G		non_coding_transcript_exon	Exon 11 of 15	ENSP00000419142.2	F8WF72
	CFAP20DC	ENST00000468415.6	TSL:1	n.*682C>G		3_prime_UTR	Exon 11 of 15	ENSP00000419142.2	F8WF72

Frequencies

GnomAD3 genomes AF: 0.00241 AC: 367 AN: 152152 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00176

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00339 AC: 839 AN: 247350 AF XY: 0.00386

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.0255

Gnomad EAS exome AF: 0.0000551

Gnomad FIN exome AF: 0.0000927

Gnomad NFE exome AF: 0.00228

Gnomad OTH exome AF: 0.00447

GnomAD4 exome AF: 0.00222 AC: 3228 AN: 1456596 Hom.: 20 Cov.: 28 AF XY: 0.00251 AC XY: 1822 AN XY: 724556

African (AFR) AF: 0.000271 AC: 9 AN: 33232

American (AMR) AF: 0.00236 AC: 103 AN: 43648

Ashkenazi Jewish (ASJ) AF: 0.0260 AC: 674 AN: 25962

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00794 AC: 676 AN: 85134

European-Finnish (FIN) AF: 0.0000937 AC: 5 AN: 53376

Middle Eastern (MID) AF: 0.0105 AC: 60 AN: 5724

European-Non Finnish (NFE) AF: 0.00131 AC: 1457 AN: 1109750

Other (OTH) AF: 0.00405 AC: 244 AN: 60200

GnomAD4 genome AF: 0.00241 AC: 367 AN: 152270 Hom.: 1 Cov.: 32 AF XY: 0.00261 AC XY: 194 AN XY: 74460

African (AFR) AF: 0.000241 AC: 10 AN: 41548

American (AMR) AF: 0.00438 AC: 67 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00176 AC: 120 AN: 68016

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00472 Hom.: 2

Bravo AF: 0.00229

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00395 AC: 34

ExAC AF: 0.00318 AC: 386

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00404

EpiControl AF: 0.00381

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	0.98
Eigen	Benign	0.14
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.2
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.057
Sift	Benign	0.12	T
Sift4G	Benign	0.87	T
Polyphen		0.34	B
Vest4		0.18
MVP		0.20
MPC		0.14
ClinPred		0.034	T
GERP RS		5.0
gMVP		0.29
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs139315615; hg19: chr3-58852298; COSMIC: COSV105162616;