dbSNP rs151205971: CFAP69:p.Arg106His (chr7-90262017-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001039706.3(CFAP69):c.317G>A(p.Arg106His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,602,988 control chromosomes in the GnomAD database, including 24 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R106S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0081 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 11 hom. )

Consequence

CFAP69
NM_001039706.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.15

Publications

4 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=0.0031071007).

BP6

Variant 7-90262017-G-A is Benign according to our data. Variant chr7-90262017-G-A is described in ClinVar as Benign. ClinVar VariationId is 712004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00812 (1235/152168) while in subpopulation AFR AF = 0.0278 (1152/41512). AF 95% confidence interval is 0.0264. There are 13 homozygotes in GnomAd4. There are 577 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039706.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP69	NM_001039706.3	MANE Select	c.317G>A	p.Arg106His	missense	Exon 4 of 23	NP_001034795.2	A5D8W1-1
CFAP69	NM_001160138.2		c.317G>A	p.Arg106His	missense	Exon 4 of 23	NP_001153610.1	A5D8W1-5
CFAP69	NM_001363438.1		c.317G>A	p.Arg106His	missense	Exon 4 of 22	NP_001350367.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP69	ENST00000389297.8	TSL:1 MANE Select	c.317G>A	p.Arg106His	missense	Exon 4 of 23	ENSP00000373948.4	A5D8W1-1
CFAP69	ENST00000497910.5	TSL:2	c.317G>A	p.Arg106His	missense	Exon 4 of 23	ENSP00000419549.1	A5D8W1-5
CFAP69	ENST00000949775.1		c.317G>A	p.Arg106His	missense	Exon 4 of 22	ENSP00000619834.1

Frequencies

GnomAD3 genomes

AF:

0.00811

AC:

1233

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00199

AC:

479

AN:

240566

AF XY:

0.00162

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000580

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000904

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.000791

AC:

1147

AN:

1450820

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

495

AN XY:

721520

show subpopulations

African (AFR)

AF:

0.0269

AC:

880

AN:

32766

American (AMR)

AF:

0.00168

AC:

AN:

42754

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25936

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39200

South Asian (SAS)

AF:

0.0000359

AC:

AN:

83640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53234

Middle Eastern (MID)

AF:

0.000523

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000795

AC:

AN:

1107596

Other (OTH)

AF:

0.00167

AC:

100

AN:

59956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

102

153

204

255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00812

AC:

1235

AN:

152168

Hom.:

Cov.:

AF XY:

0.00775

AC XY:

577

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0278

AC:

1152

AN:

41512

American (AMR)

AF:

0.00307

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67990

Other (OTH)

AF:

0.0109

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

120

180

240

300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00295

Hom.:

Bravo

AF:

0.00912

ESP6500AA

AF:

0.0258

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00256

AC:

309

Asia WGS

AF:

0.00318

AC:

AN:

3472

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

CFAP69-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.73

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

PhyloP100

-1.1

PROVEAN

Benign

-0.040

REVEL

Benign

0.0

Sift

Benign

0.17

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.14

MVP

0.014

MPC

0.078

ClinPred

0.0067

GERP RS

-9.2

Varity_R

0.025

gMVP

0.088

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over