Genetic Variant CFAP20DC:p.Val512Met (chr3-58863617-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001394063.1(CFAP20DC):c.1534G>A(p.Val512Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 1,614,166 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 16 hom. )

Consequence

CFAP20DC
NM_001394063.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.504

Publications

6 publications found

Variant links:

Genes affected

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

CFAP20DC links:

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

CFAP20DC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005091518).

BP6

Variant 3-58863617-C-T is Benign according to our data. Variant chr3-58863617-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 981127.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP20DC	NM_001394063.1	MANE Select	c.1534G>A	p.Val512Met	missense	Exon 12 of 17	NP_001380992.1	A0A2U3TZK7
CFAP20DC	NM_001351530.2		c.1369G>A	p.Val457Met	missense	Exon 11 of 16	NP_001338459.1
CFAP20DC	NM_001351531.2		c.919G>A	p.Val307Met	missense	Exon 11 of 16	NP_001338460.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP20DC	ENST00000482387.7	TSL:5 MANE Select	c.1534G>A	p.Val512Met	missense	Exon 12 of 17	ENSP00000417122.2	A0A2U3TZK7
CFAP20DC	ENST00000468415.6	TSL:1	n.*964G>A		non_coding_transcript_exon	Exon 12 of 15	ENSP00000419142.2	F8WF72
CFAP20DC	ENST00000468415.6	TSL:1	n.*964G>A		3_prime_UTR	Exon 12 of 15	ENSP00000419142.2	F8WF72

Frequencies

GnomAD3 genomes

AF:

0.00229

AC:

349

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00397

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00159

AC:

400

AN:

251290

AF XY:

0.00160

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000867

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00278

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00375

AC:

5481

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

2637

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.000358

AC:

AN:

33480

American (AMR)

AF:

0.000872

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00272

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000197

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000318

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00452

AC:

5030

AN:

1112000

Other (OTH)

AF:

0.00480

AC:

290

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

292

584

876

1168

1460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00229

AC:

349

AN:

152290

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000987

AC:

AN:

41548

American (AMR)

AF:

0.00137

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00397

AC:

270

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00299

Hom.:

Bravo

AF:

0.00233

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00146

AC:

177

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00447

EpiControl

AF:

0.00373

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.0

(source)

DANN

Benign

0.94

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.82

M_CAP

Benign

0.0099

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-0.50

PROVEAN

Benign

-0.11

REVEL

Benign

0.061

Sift

Benign

0.31

Sift4G

Benign

0.24

Polyphen

0.0060

Vest4

0.10

MVP

0.11

MPC

0.15

ClinPred

0.011

GERP RS

0.55

gMVP

0.072

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over