Genetic Variant CFAP69:p.Arg106Ser (chr7-90262016-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001039706.3(CFAP69):c.316C>A(p.Arg106Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000381 in 1,603,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R106H) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

CFAP69
NM_001039706.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.229

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029229552).

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.316C>A	p.Arg106Ser	missense	Exon 4 of 23	NP_001034795.2	A5D8W1-1
CFAP69	NM_001160138.2		c.316C>A	p.Arg106Ser	missense	Exon 4 of 23	NP_001153610.1	A5D8W1-5
CFAP69	NM_001363438.1		c.316C>A	p.Arg106Ser	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.316C>A	p.Arg106Ser	missense	Exon 4 of 23	ENSP00000373948.4	A5D8W1-1
CFAP69	ENST00000497910.5	TSL:2	c.316C>A	p.Arg106Ser	missense	Exon 4 of 23	ENSP00000419549.1	A5D8W1-5
CFAP69	ENST00000949775.1		c.316C>A	p.Arg106Ser	missense	Exon 4 of 22	ENSP00000619834.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000249

AC:

AN:

240586

AF XY:

0.0000153

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000202

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000271

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000400

AC:

AN:

1451040

Hom.:

Cov.:

AF XY:

0.0000471

AC XY:

AN XY:

721652

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32788

American (AMR)

AF:

0.00

AC:

AN:

42782

Ashkenazi Jewish (ASJ)

AF:

0.000578

AC:

AN:

25946

East Asian (EAS)

AF:

0.00

AC:

AN:

39200

South Asian (SAS)

AF:

0.0000837

AC:

AN:

83618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53238

Middle Eastern (MID)

AF:

0.000697

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000181

AC:

AN:

1107770

Other (OTH)

AF:

0.000200

AC:

AN:

59960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000249

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.32

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.0058

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.40

M_CAP

Benign

0.0076

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

PhyloP100

0.23

PROVEAN

Benign

0.26

REVEL

Benign

0.025

Sift

Benign

0.64

Sift4G

Benign

0.78

Polyphen

0.0

Vest4

0.20

MutPred

0.33

Gain of disorder (P = 0.0426)

MVP

0.048

MPC

0.082

ClinPred

0.019

GERP RS

-1.9

Varity_R

0.086

gMVP

0.11

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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