18-50251567-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145020.5(CFAP53):c.691C>T(p.Arg231Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,614,156 control chromosomes in the GnomAD database, including 7,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 869 hom., cov: 33)

Exomes 𝑓: 0.028 ( 6473 hom. )

Consequence

CFAP53
NM_145020.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.04

Publications

14 publications found

Variant links:

Genes affected

CFAP53 (HGNC:26530): (cilia and flagella associated protein 53) This gene belongs to the CFAP53 family. It was found to be differentially expressed by the ciliated cells of frog epidermis and in skin fibroblasts from human. Mutations in this gene are associated with visceral heterotaxy-6, which implicates this gene in determination of left-right asymmetric patterning. [provided by RefSeq, Aug 2015]

CFAP53 Gene-Disease associations (from GenCC):

heterotaxy, visceral, 6, autosomal
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
situs inversus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CFAP53 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031661391).

BP6

Variant 18-50251567-G-A is Benign according to our data. Variant chr18-50251567-G-A is described in ClinVar as Benign. ClinVar VariationId is 262556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP53	NM_145020.5 link	c.691C>T	p.Arg231Cys	missense_variant	Exon 4 of 8	ENST00000398545.5	NP_659457.2	Q96M91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5 link	c.691C>T	p.Arg231Cys	missense_variant	Exon 4 of 8	1	NM_145020.5	ENSP00000381553.3		Q96M91

Frequencies

GnomAD3 genomes

AF:

0.0410

AC:

6239

AN:

152170

Hom.:

863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00596

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.446

Gnomad SAS

AF:

0.0655

Gnomad FIN

AF:

0.0360

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00370

Gnomad OTH

AF:

0.0454

GnomAD2 exomes

AF:

0.0835

AC:

20839

AN:

249570

AF XY:

0.0726

show subpopulations

Gnomad AFR exome

AF:

0.00517

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.448

Gnomad FIN exome

AF:

0.0334

Gnomad NFE exome

AF:

0.00416

Gnomad OTH exome

AF:

0.0551

GnomAD4 exome

AF:

0.0285

AC:

41629

AN:

1461868

Hom.:

6473

Cov.:

AF XY:

0.0280

AC XY:

20361

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00397

AC:

133

AN:

33478

American (AMR)

AF:

0.258

AC:

11557

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0185

AC:

483

AN:

26136

East Asian (EAS)

AF:

0.470

AC:

18654

AN:

39700

South Asian (SAS)

AF:

0.0544

AC:

4696

AN:

86258

European-Finnish (FIN)

AF:

0.0334

AC:

1782

AN:

53402

Middle Eastern (MID)

AF:

0.00971

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00182

AC:

2019

AN:

1112008

Other (OTH)

AF:

0.0372

AC:

2249

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

2037

4074

6112

8149

10186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.0411

AC:

6255

AN:

152288

Hom.:

869

Cov.:

AF XY:

0.0478

AC XY:

3562

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00594

AC:

247

AN:

41564

American (AMR)

AF:

0.169

AC:

2589

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3470

East Asian (EAS)

AF:

0.446

AC:

2304

AN:

5166

South Asian (SAS)

AF:

0.0661

AC:

319

AN:

4824

European-Finnish (FIN)

AF:

0.0360

AC:

382

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00370

AC:

252

AN:

68036

Other (OTH)

AF:

0.0459

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

239

478

718

957

1196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0265

Hom.:

2251

Bravo

AF:

0.0528

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00486

AC:

ESP6500EA

AF:

0.00381

AC:

ExAC

AF:

0.0734

AC:

8885

Asia WGS

AF:

0.227

AC:

786

AN:

3478

EpiCase

AF:

0.00202

EpiControl

AF:

0.00202

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Heterotaxy, visceral, 6, autosomal

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.93

PhyloP100

3.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

REVEL

Benign

0.13

Sift

Benign

0.044

Sift4G

Uncertain

0.0050

Polyphen

0.13

Vest4

0.24

MPC

0.43

ClinPred

0.022

GERP RS

1.3

Varity_R

0.087

gMVP

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over