7-90282987-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001039706.3(CFAP69):c.1468G>A(p.Val490Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 1,593,122 control chromosomes in the GnomAD database, including 500,608 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51207 hom., cov: 32)

Exomes 𝑓: 0.79 ( 449401 hom. )

Consequence

CFAP69
NM_001039706.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.58

Publications

39 publications found

Variant links:

Genes affected

CFAP69 (HGNC:26107): (cilia and flagella associated protein 69) Acts upstream of or within sperm axoneme assembly. Located in cytoplasm and sperm midpiece. Implicated in spermatogenic failure 24. [provided by Alliance of Genome Resources, Apr 2022]

CFAP69 Gene-Disease associations (from GenCC):

non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
spermatogenic failure 24
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CFAP69 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.298084E-7).

BP6

Variant 7-90282987-G-A is Benign according to our data. Variant chr7-90282987-G-A is described in ClinVar as Benign. ClinVar VariationId is 1192635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP69	NM_001039706.3 link	c.1468G>A	p.Val490Met	missense_variant	Exon 13 of 23	ENST00000389297.8	NP_001034795.2	A5D8W1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP69	ENST00000389297.8 link	c.1468G>A	p.Val490Met	missense_variant	Exon 13 of 23	1	NM_001039706.3	ENSP00000373948.4		A5D8W1-1

Frequencies

GnomAD3 genomes

AF:

0.818

AC:

124433

AN:

152084

Hom.:

51169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.854

Gnomad AMI

AF:

0.803

Gnomad AMR

AF:

0.827

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.870

Gnomad FIN

AF:

0.869

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.808

GnomAD2 exomes

AF:

0.825

AC:

194826

AN:

236084

AF XY:

0.821

show subpopulations

Gnomad AFR exome

AF:

0.855

Gnomad AMR exome

AF:

0.866

Gnomad ASJ exome

AF:

0.780

Gnomad EAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.864

Gnomad NFE exome

AF:

0.773

Gnomad OTH exome

AF:

0.802

GnomAD4 exome

AF:

0.788

AC:

1135454

AN:

1440920

Hom.:

449401

Cov.:

AF XY:

0.790

AC XY:

565961

AN XY:

716760

show subpopulations

African (AFR)

AF:

0.856

AC:

27660

AN:

32312

American (AMR)

AF:

0.864

AC:

35994

AN:

41678

Ashkenazi Jewish (ASJ)

AF:

0.781

AC:

19995

AN:

25600

East Asian (EAS)

AF:

0.999

AC:

38226

AN:

38272

South Asian (SAS)

AF:

0.857

AC:

71014

AN:

82850

European-Finnish (FIN)

AF:

0.863

AC:

45650

AN:

52896

Middle Eastern (MID)

AF:

0.796

AC:

4535

AN:

5696

European-Non Finnish (NFE)

AF:

0.767

AC:

844907

AN:

1102228

Other (OTH)

AF:

0.799

AC:

47473

AN:

59388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

11538

23076

34613

46151

57689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20432

40864

61296

81728

102160

<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:

0.818

AC:

124523

AN:

152202

Hom.:

51207

Cov.:

AF XY:

0.823

AC XY:

61260

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.853

AC:

35436

AN:

41522

American (AMR)

AF:

0.827

AC:

12630

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.792

AC:

2749

AN:

3470

East Asian (EAS)

AF:

0.997

AC:

5161

AN:

5178

South Asian (SAS)

AF:

0.871

AC:

4200

AN:

4824

European-Finnish (FIN)

AF:

0.869

AC:

9210

AN:

10596

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.771

AC:

52450

AN:

68018

Other (OTH)

AF:

0.810

AC:

1714

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1160

2320

3479

4639

5799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.787

Hom.:

156351

Bravo

AF:

0.816

TwinsUK

AF:

0.765

AC:

2835

ALSPAC

AF:

0.756

AC:

2915

ESP6500AA

AF:

0.860

AC:

3256

ESP6500EA

AF:

0.766

AC:

6284

ExAC

AF:

0.829

AC:

100155

Asia WGS

AF:

0.931

AC:

3233

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

CFAP69-related disorder

Benign:1

Oct 16, 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). -

Spermatogenic failure 24

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.10

DEOGEN2

Benign

0.013

T;.;.;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.38

T;T;T;T

MetaRNN

Benign

5.3e-7

T;T;T;T

MetaSVM

Benign

-0.95

PhyloP100

1.6

PROVEAN

Benign

0.23

N;N;N;N

REVEL

Benign

0.088

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.010

B;B;.;.

Vest4

0.038

MPC

0.064

ClinPred

0.0036

GERP RS

4.2

Varity_R

0.042

gMVP

0.21

Mutation Taster

=100/0

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