Variant 7-90255438-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001039706.3(CFAP69):c.136A>G(p.Met46Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,612,780 control chromosomes in the GnomAD database, including 8 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 7 hom. )

Consequence

CFAP69
NM_001039706.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.20

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010617822).

BP6

Variant 7-90255438-A-G is Benign according to our data. Variant chr7-90255438-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3044692.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP69	NM_001039706.3 linkuse as main transcript	c.136A>G	p.Met46Val	missense_variant	2/23	ENST00000389297.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP69	ENST00000389297.8 linkuse as main transcript	c.136A>G	p.Met46Val	missense_variant	2/23	1	NM_001039706.3	P1	A5D8W1-1

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

351

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00315

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00201

AC:

500

AN:

249146

Hom.:

AF XY:

0.00197

AC XY:

267

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.000775

Gnomad AMR exome

AF:

0.00247

Gnomad ASJ exome

AF:

0.00487

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000514

Gnomad NFE exome

AF:

0.00286

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00308

AC:

4505

AN:

1460432

Hom.:

Cov.:

AF XY:

0.00292

AC XY:

2119

AN XY:

726574

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.00395

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000395

Gnomad4 NFE exome

AF:

0.00369

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.00230

AC:

351

AN:

152348

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

162

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00315

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00246

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00110

AC:

ESP6500EA

AF:

0.00331

AC:

ExAC

AF:

0.00170

AC:

206

EpiCase

AF:

0.00328

EpiControl

AF:

0.00302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CFAP69-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 11, 2023

This variant is classified as likely 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

0.059

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.5

DANN

Benign

0.52

DEOGEN2

Benign

0.0087

T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.97

N;N;N

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.018

Sift

Benign

0.48

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.0

B;B

Vest4

0.23

MVP

0.15

MPC

0.067

ClinPred

0.0058

GERP RS

1.0

Varity_R

0.056

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over