Variant 12-113151961-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001144872.3(CFAP73):c.100C>T(p.Arg34Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,551,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CFAP73
NM_001144872.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.204

Variant links:

Genes affected

CFAP73 (HGNC:37100): (cilia and flagella associated protein 73) Predicted to enable dynein complex binding activity. Predicted to be involved in cilium movement and inner dynein arm assembly. Predicted to be located in axonemal outer doublet and motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

CFAP73 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25182414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP73	NM_001144872.3 linkuse as main transcript	c.100C>T	p.Arg34Cys	missense_variant	2/8	ENST00000335621.11	NP_001138344.1	A6NFT4
CFAP73	XM_011538327.3 linkuse as main transcript	c.100C>T	p.Arg34Cys	missense_variant	2/7		XP_011536629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP73	ENST00000335621.11 linkuse as main transcript	c.100C>T	p.Arg34Cys	missense_variant	2/8	5	NM_001144872.3	ENSP00000333915.6		A6NFT4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

156226

Hom.:

AF XY:

0.0000242

AC XY:

AN XY:

82808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000331

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1399292

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

690158

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000505

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000139

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.100C>T (p.R34C) alteration is located in exon 2 (coding exon 2) of the CFAP73 gene. This alteration results from a C to T substitution at nucleotide position 100, causing the arginine (R) at amino acid position 34 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.66

M_CAP

Benign

0.012

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.19

PROVEAN

Pathogenic

-6.1

REVEL

Benign

0.032

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.083

MutPred

0.41

Gain of catalytic residue at L35 (P = 0.0081);

MVP

0.50

ClinPred

0.66

GERP RS

0.40

Varity_R

0.17

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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