rs1029365

chr7-90282987-G-Achr7-90282987-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.82 (51207 hom., cov: 32)
  • Exomes 𝑓: 0.79 (449401 hom.)
• Consequence: CFAP69 NM_001039706.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.58

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
CFAP69	NM_001039706.3	c.1468G>A	p.Val490Met	missense_variant	13/23	ENST00000389297.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP69	ENST00000389297.8	c.1468G>A	p.Val490Met	missense_variant	13/23	1	NM_001039706.3	P1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124433 AN: 152084 Hom.: 51169 Cov.: 32

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

GnomAD3 exomes AF: 0.825 AC: 194826 AN: 236084 Hom.: 80806 AF XY: 0.821 AC XY: 105738 AN XY: 128718

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 SAS exome AF: 0.858

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.: 37 AF XY: 0.790 AC XY: 565961 AN XY: 716760

Gnomad4 AFR exome AF: 0.856

Gnomad4 AMR exome AF: 0.864

Gnomad4 ASJ exome AF: 0.781

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.857

Gnomad4 FIN exome AF: 0.863

Gnomad4 NFE exome AF: 0.767

Gnomad4 OTH exome AF: 0.799

GnomAD4 genome AF: 0.818 AC: 124523 AN: 152202 Hom.: 51207 Cov.: 32 AF XY: 0.823 AC XY: 61260 AN XY: 74408

Gnomad4 AFR AF: 0.853

Gnomad4 AMR AF: 0.827

Gnomad4 ASJ AF: 0.792

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.810

Alfa AF: 0.782 Hom.: 110995

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CFAP69-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	16
Dann	Benign	0.10
DEOGEN2	Benign	0.013	T;.;.;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.38	T;T;T;T
MetaRNN	Benign	5.3e-7	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P;P;P
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	T
GERP RS		4.2
Varity_R		0.042
gMVP		0.21

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

LitVar

Other links and lift over

dbSNP: rs1029365; hg19: chr7-89912301; COSMIC: COSV60188858;