dbSNP rs201631766: CFAP69:p.His168Asn (chr7-90268354-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039706.3(CFAP69):c.502C>A(p.His168Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,886 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H168Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CFAP69
NM_001039706.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

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:

ENSG00000234459 (HGNC:):

ENSG00000234459 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18021274).

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.502C>A	p.His168Asn	missense	Exon 6 of 23	NP_001034795.2	A5D8W1-1
CFAP69	NM_001363438.1		c.502C>A	p.His168Asn	missense	Exon 6 of 22	NP_001350367.1
CFAP69	NM_001160138.2		c.478+24C>A		intron	N/A	NP_001153610.1	A5D8W1-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP69	ENST00000389297.8	TSL:1 MANE Select	c.502C>A	p.His168Asn	missense	Exon 6 of 23	ENSP00000373948.4	A5D8W1-1
CFAP69	ENST00000949772.1		c.502C>A	p.His168Asn	missense	Exon 6 of 21	ENSP00000619831.1
CFAP69	ENST00000867385.1		c.502C>A	p.His168Asn	missense	Exon 6 of 21	ENSP00000537444.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33368

American (AMR)

AF:

0.00

AC:

AN:

44040

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.00

AC:

AN:

85488

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110364

Other (OTH)

AF:

0.00

AC:

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.028

Eigen

Benign

0.083

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.66

M_CAP

Benign

0.0031

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

PhyloP100

1.4

PROVEAN

Benign

-1.1

REVEL

Benign

0.046

Sift

Benign

0.33

Sift4G

Benign

0.30

Polyphen

0.095

Vest4

0.24

MutPred

0.26

Loss of catalytic residue at E170 (P = 0.0881)

MVP

0.37

MPC

0.075

ClinPred

0.34

GERP RS

5.7

Varity_R

0.17

gMVP

0.19

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over