dbSNP rs10883979: CFAP43:p.Ile393Thr (chr10-104197956-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_025145.7(CFAP43):c.1178T>C(p.Ile393Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,612,784 control chromosomes in the GnomAD database, including 3,284 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.051 ( 246 hom., cov: 33)

Exomes 𝑓: 0.058 ( 3038 hom. )

Consequence

CFAP43
NM_025145.7 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.883

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

spermatogenic failure 19
Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, Ambry Genetics
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
normal pressure hydrocephalus
Inheritance: AD Classification: LIMITED Submitted by: ClinGen, Ambry Genetics
primary ciliary dyskinesia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

CFAP43 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013535917).

BP6

Variant 10-104197956-A-G is Benign according to our data. Variant chr10-104197956-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059847.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP43	NM_025145.7 link	c.1178T>C	p.Ile393Thr	missense_variant	Exon 9 of 38	ENST00000357060.8	NP_079421.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CFAP43	ENST00000357060.8 link	c.1178T>C	p.Ile393Thr	missense_variant	Exon 9 of 38	1	NM_025145.7	ENSP00000349568.3
CFAP43	ENST00000278064.7 link	c.1181T>C	p.Ile394Thr	missense_variant	Exon 9 of 22	1		ENSP00000278064.3
CFAP43	ENST00000369720.6 link	c.1181T>C	p.Ile394Thr	missense_variant	Exon 9 of 11	1		ENSP00000358734.2

Frequencies

GnomAD3 genomes

AF:

0.0506

AC:

7697

AN:

152192

Hom.:

243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0424

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0446

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.0149

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0505

Gnomad OTH

AF:

0.0532

GnomAD2 exomes

AF:

0.0631

AC:

15848

AN:

251048

AF XY:

0.0664

show subpopulations

Gnomad AFR exome

AF:

0.0441

Gnomad AMR exome

AF:

0.0419

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.0164

Gnomad NFE exome

AF:

0.0537

Gnomad OTH exome

AF:

0.0550

GnomAD4 exome

AF:

0.0577

AC:

84280

AN:

1460474

Hom.:

3038

Cov.:

AF XY:

0.0599

AC XY:

43500

AN XY:

726550

show subpopulations

African (AFR)

AF:

0.0434

AC:

1452

AN:

33450

American (AMR)

AF:

0.0415

AC:

1854

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

3046

AN:

26114

East Asian (EAS)

AF:

0.0910

AC:

3607

AN:

39640

South Asian (SAS)

AF:

0.126

AC:

10848

AN:

86136

European-Finnish (FIN)

AF:

0.0175

AC:

934

AN:

53410

Middle Eastern (MID)

AF:

0.0718

AC:

414

AN:

5766

European-Non Finnish (NFE)

AF:

0.0523

AC:

58092

AN:

1110940

Other (OTH)

AF:

0.0669

AC:

4033

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

3388

6776

10163

13551

16939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2314

4628

6942

9256

11570

<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:

0.0507

AC:

7720

AN:

152310

Hom.:

246

Cov.:

AF XY:

0.0505

AC XY:

3765

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0424

AC:

1764

AN:

41560

American (AMR)

AF:

0.0446

AC:

683

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

361

AN:

3472

East Asian (EAS)

AF:

0.103

AC:

534

AN:

5182

South Asian (SAS)

AF:

0.132

AC:

637

AN:

4830

European-Finnish (FIN)

AF:

0.0149

AC:

158

AN:

10624

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0506

AC:

3440

AN:

68026

Other (OTH)

AF:

0.0602

AC:

127

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

391

782

1172

1563

1954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0567

Hom.:

924

Bravo

AF:

0.0515

TwinsUK

AF:

0.0491

AC:

182

ALSPAC

AF:

0.0576

AC:

222

ESP6500AA

AF:

0.0397

AC:

175

ESP6500EA

AF:

0.0548

AC:

471

ExAC

AF:

0.0640

AC:

7764

Asia WGS

AF:

0.147

AC:

511

AN:

3478

EpiCase

AF:

0.0537

EpiControl

AF:

0.0552

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CFAP43-related disorder

Benign:1

Jul 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.084

T;T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.44

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

0.88

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.069

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.047

MPC

0.17

ClinPred

0.0030

GERP RS

2.2

Varity_R

0.054

gMVP

0.38

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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