Variant 10-104143495-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_025145.7(CFAP43):c.4089A>C(p.Glu1363Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000932 in 1,614,112 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 3 hom. )

Consequence

CFAP43
NM_025145.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.831

Variant links:

Genes affected

CFAP43 (HGNC:26684): (cilia and flagella associated protein 43) This gene encodes a member of the cilia- and flagella-associated protein family. [provided by RefSeq, Sep 2016]

CFAP43 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045016676).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000434 (66/152236) while in subpopulation NFE AF= 0.000808 (55/68038). AF 95% confidence interval is 0.000638. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP43	NM_025145.7 link	c.4089A>C	p.Glu1363Asp	missense_variant	32/38	ENST00000357060.8	NP_079421.5	Q8NDM7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CFAP43	ENST00000357060.8 link	c.4089A>C	p.Glu1363Asp	missense_variant	32/38	1	NM_025145.7	ENSP00000349568.3	Q8NDM7-1
CFAP43	ENST00000434629.5 link	c.2082A>C	p.Glu694Asp	missense_variant	17/23	1		ENSP00000391364.1	H7BZT8
CFAP43	ENST00000457071.5 link	c.633A>C	p.Glu211Asp	missense_variant	6/12	2		ENSP00000394274.1	H0Y4U9

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000808

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000398

AC:

100

AN:

251366

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000827

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000984

AC:

1438

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000965

AC XY:

702

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000434

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000808

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000744

Hom.:

Bravo

AF:

0.000385

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000771

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

Sep 16, 2021

The c.4089A>C (p.E1363D) alteration is located in exon 32 (coding exon 32) of the CFAP43 gene. This alteration results from a A to C substitution at nucleotide position 4089, causing the glutamic acid (E) at amino acid position 1363 to be replaced by an aspartic acid (D). 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

0.13

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

Eigen

Benign

0.049

Eigen_PC

Benign

0.083

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.64

M_CAP

Benign

0.018

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.76

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

REVEL

Benign

0.014

Sift

Benign

0.11

Sift4G

Benign

0.12

Polyphen

0.18

Vest4

0.10

MutPred

0.21

Loss of helix (P = 0.1299);

MVP

0.23

MPC

0.12

ClinPred

0.023

GERP RS

2.0

Varity_R

0.084

gMVP

0.19

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