18-50261232-C-T

Variant summary

Our verdict is Benign. Variant got -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 (★★).

Frequency

Genomes: 𝑓 0.0066 ( 8 hom., cov: 28)
Exomes 𝑓: 0.00067 ( 11 hom. )

Consequence

CFAP53
NM_145020.5 missense

Scores

3
4
10

Clinical Significance

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

Conservation

PhyloP100: 2.46
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 262551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-50261232-C-T is described in Lovd as [Benign].
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 male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CFAP53NM_145020.5 linkuse as main transcriptc.305G>A p.Arg102His missense_variant 3/8 ENST00000398545.5 NP_659457.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CFAP53ENST00000398545.5 linkuse as main transcriptc.305G>A p.Arg102His missense_variant 3/81 NM_145020.5 ENSP00000381553 P1

Frequencies

GnomAD3 genomes
AF:
0.00656
AC:
908
AN:
138392
Hom.:
8
Cov.:
28
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
GnomAD3 exomes
AF:
0.00197
AC:
281
AN:
142736
Hom.:
4
AF XY:
0.00147
AC XY:
119
AN XY:
80892
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 SAS exome
AF:
0.000115
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.:
11
Cov.:
36
AF XY:
0.000614
AC XY:
401
AN XY:
652692
show subpopulations
Gnomad4 AFR exome
AF:
0.0232
Gnomad4 AMR exome
AF:
0.00167
Gnomad4 ASJ exome
AF:
0.000462
Gnomad4 EAS exome
AF:
0.0000590
Gnomad4 SAS exome
AF:
0.000234
Gnomad4 FIN exome
AF:
0.0000924
Gnomad4 NFE exome
AF:
0.0000827
Gnomad4 OTH exome
AF:
0.00170
GnomAD4 genome
AF:
0.00662
AC:
916
AN:
138446
Hom.:
8
Cov.:
28
AF XY:
0.00614
AC XY:
407
AN XY:
66258
show subpopulations
Gnomad4 AFR
AF:
0.0233
Gnomad4 AMR
AF:
0.00367
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000122
Gnomad4 OTH
AF:
0.00591
Alfa
AF:
0.000793
Hom.:
3
ESP6500AA
AF:
0.0179
AC:
64
ESP6500EA
AF:
0.000492
AC:
4
ExAC
AF:
0.00225
AC:
271
Asia WGS
AF:
0.00173
AC:
6
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
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsOct 26, 2021- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 12, 2024- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.42
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.15
T
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.84
T
MetaRNN
Benign
0.0078
T
MetaSVM
Benign
-0.96
T
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.13
Sift
Uncertain
0.012
D
Sift4G
Uncertain
0.029
D
Polyphen
1.0
D
Vest4
0.47
MVP
0.49
MPC
0.42
ClinPred
0.037
T
GERP RS
6.1
Varity_R
0.19
gMVP
0.057

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

LitVar

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

Other links and lift over

dbSNP: rs76722120; hg19: chr18-47787602; API