18-50238676-G-T

Position:

chr18-50238676-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_145020.5(CFAP53):c.1243C>A(p.Arg415Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,610,594 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

CFAP53
NM_145020.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.32

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009191483).

BP6

Variant 18-50238676-G-T is Benign according to our data. Variant chr18-50238676-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2648715.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000145 (22/152222) while in subpopulation SAS AF= 0.00124 (6/4820). AF 95% confidence interval is 0.000542. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP53	NM_145020.5 linkuse as main transcript	c.1243C>A	p.Arg415Ser	missense_variant	7/8	ENST00000398545.5	NP_659457.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5 linkuse as main transcript	c.1243C>A	p.Arg415Ser	missense_variant	7/8	1	NM_145020.5	ENSP00000381553	P1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000289

AC:

AN:

245546

Hom.:

AF XY:

0.000360

AC XY:

AN XY:

133334

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000604

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000979

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.000204

AC:

298

AN:

1458372

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

181

AN XY:

725472

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000145

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.000132

ExAC

AF:

0.000240

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000551

EpiControl

AF:

0.000120

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.1243C>A (p.R415S) alteration is located in exon 7 (coding exon 7) of the CCDC11 gene. This alteration results from a C to A substitution at nucleotide position 1243, causing the arginine (R) at amino acid position 415 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

CFAP53: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.0015

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.51

M_CAP

Benign

0.0044

MetaRNN

Benign

0.0092

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.050

REVEL

Benign

0.032

Sift

Benign

0.64

Sift4G

Benign

0.14

Polyphen

0.28

Vest4

0.29

MVP

0.072

MPC

0.14

ClinPred

0.025

GERP RS

2.8

Varity_R

0.075

gMVP

0.087

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over