18-50261232-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_145020.5(CFAP53):c.305G>A(p.Arg102His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,461,570 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R102C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0066 ( 8 hom., cov: 28)

Exomes 𝑓: 0.00067 ( 11 hom. )

Consequence

CFAP53
NM_145020.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.46

Publications

2 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=0.007839054).

BP6

Variant 18-50261232-C-T is Benign according to our data. Variant chr18-50261232-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00662 (916/138446) while in subpopulation AFR AF = 0.0233 (849/36492). AF 95% confidence interval is 0.022. There are 8 homozygotes in GnomAd4. There are 407 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP53	NM_145020.5 link	c.305G>A	p.Arg102His	missense_variant	Exon 3 of 8	ENST00000398545.5	NP_659457.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5 link	c.305G>A	p.Arg102His	missense_variant	Exon 3 of 8	1	NM_145020.5	ENSP00000381553.3

Frequencies

GnomAD3 genomes

AF:

0.00656

AC:

908

AN:

138392

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00375

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:

0.000122

Gnomad OTH

AF:

0.00597

GnomAD2 exomes

AF:

0.00197

AC:

281

AN:

142736

AF XY:

0.00147

show subpopulations

Gnomad AFR exome

AF:

0.0255

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.000180

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000725

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000667

AC:

883

AN:

1323124

Hom.:

Cov.:

AF XY:

0.000614

AC XY:

401

AN XY:

652692

show subpopulations

African (AFR)

AF:

0.0232

AC:

632

AN:

27278

American (AMR)

AF:

0.00167

AC:

AN:

22212

Ashkenazi Jewish (ASJ)

AF:

0.000462

AC:

AN:

21644

East Asian (EAS)

AF:

0.0000590

AC:

AN:

33926

South Asian (SAS)

AF:

0.000234

AC:

AN:

63986

European-Finnish (FIN)

AF:

0.0000924

AC:

AN:

43304

Middle Eastern (MID)

AF:

0.000985

AC:

AN:

4062

European-Non Finnish (NFE)

AF:

0.0000827

AC:

AN:

1052510

Other (OTH)

AF:

0.00170

AC:

AN:

54202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.423

Heterozygous variant carriers

118

158

197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00662

AC:

916

AN:

138446

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

407

AN XY:

66258

show subpopulations

African (AFR)

AF:

0.0233

AC:

849

AN:

36492

American (AMR)

AF:

0.00367

AC:

AN:

13080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3394

East Asian (EAS)

AF:

0.00

AC:

AN:

4830

South Asian (SAS)

AF:

0.00

AC:

AN:

4320

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.000122

AC:

AN:

65762

Other (OTH)

AF:

0.00591

AC:

AN:

1860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

124

165

206

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:

0.00223

Hom.:

ESP6500AA

AF:

0.0179

AC:

ESP6500EA

AF:

0.000492

AC:

ExAC

AF:

0.00225

AC:

271

Asia WGS

AF:

0.00173

AC:

AN:

3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Heterotaxy, visceral, 6, autosomal

Benign:2

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 26, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.96

PhyloP100

2.5

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.13

Sift

Uncertain

0.012

Sift4G

Uncertain

0.029

Polyphen

1.0

Vest4

0.47

MVP

0.49

MPC

0.42

ClinPred

0.037

GERP RS

6.1

Varity_R

0.19

gMVP

0.057

Mutation Taster

=92/8

polymorphism

(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