Genetic Variant CFAP20DC:p.Lys367Arg (chr3-58867852-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394063.1(CFAP20DC):c.1100A>G(p.Lys367Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,613,744 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

CFAP20DC
NM_001394063.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012462199).

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.1100A>G	p.Lys367Arg	missense	Exon 10 of 17	NP_001380992.1	A0A2U3TZK7
CFAP20DC	NM_001351530.2		c.935A>G	p.Lys312Arg	missense	Exon 9 of 16	NP_001338459.1
CFAP20DC	NM_001351531.2		c.485A>G	p.Lys162Arg	missense	Exon 9 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.1100A>G	p.Lys367Arg	missense	Exon 10 of 17	ENSP00000417122.2	A0A2U3TZK7
CFAP20DC	ENST00000468415.6	TSL:1	n.*530A>G		non_coding_transcript_exon	Exon 10 of 15	ENSP00000419142.2	F8WF72
CFAP20DC	ENST00000468415.6	TSL:1	n.*530A>G		3_prime_UTR	Exon 10 of 15	ENSP00000419142.2	F8WF72

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000179

AC:

AN:

251310

AF XY:

0.000133

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000534

AC:

AN:

1461448

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727002

show subpopulations

African (AFR)

AF:

0.00182

AC:

AN:

33464

American (AMR)

AF:

0.000134

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111714

Other (OTH)

AF:

0.000182

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000552

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

41580

American (AMR)

AF:

0.000523

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000224

Hom.:

Bravo

AF:

0.000808

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.046

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.74

M_CAP

Benign

0.0082

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

1.4

PROVEAN

Benign

-0.91

REVEL

Benign

0.046

Sift

Benign

0.20

Sift4G

Benign

0.48

Polyphen

0.20

Vest4

0.14

MVP

0.29

MPC

0.11

ClinPred

0.053

GERP RS

4.4

gMVP

0.23

Mutation Taster

=84/16

polymorphism

(source)

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

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