rs1029365

Variant names:

• chr7-90282987-G-A
• rs1029365
• NM_001039706.3:c.1468G>A
• CFAP69 p.Val490Met

Your query was ambiguous. Multiple possible variants found:

• chr7-90282987-G-A
• chr7-90282987-G-T

Variant summary

Our verdict is Benign. The variant received -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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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:3
• Conservation: PhyloP100: 1.58
• Publications: 39 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP69	NM_001039706.3	MANE Select	c.1468G>A	p.Val490Met	missense	Exon 13 of 23	NP_001034795.2	A5D8W1-1
	CFAP69	NM_001160138.2		c.1414G>A	p.Val472Met	missense	Exon 13 of 23	NP_001153610.1	A5D8W1-5
	CFAP69	NM_001363438.1		c.1468G>A	p.Val490Met	missense	Exon 13 of 22	NP_001350367.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP69	ENST00000389297.8	TSL:1 MANE Select	c.1468G>A	p.Val490Met	missense	Exon 13 of 23	ENSP00000373948.4	A5D8W1-1
	CFAP69	ENST00000497910.5	TSL:2	c.1414G>A	p.Val472Met	missense	Exon 13 of 23	ENSP00000419549.1	A5D8W1-5
	CFAP69	ENST00000949775.1		c.1345G>A	p.Val449Met	missense	Exon 12 of 22	ENSP00000619834.1

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

GnomAD2 exomes AF: 0.825 AC: 194826 AN: 236084 AF XY: 0.821

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 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

African (AFR) AF: 0.856 AC: 27660 AN: 32312

American (AMR) AF: 0.864 AC: 35994 AN: 41678

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 19995 AN: 25600

East Asian (EAS) AF: 0.999 AC: 38226 AN: 38272

South Asian (SAS) AF: 0.857 AC: 71014 AN: 82850

European-Finnish (FIN) AF: 0.863 AC: 45650 AN: 52896

Middle Eastern (MID) AF: 0.796 AC: 4535 AN: 5696

European-Non Finnish (NFE) AF: 0.767 AC: 844907 AN: 1102228

Other (OTH) AF: 0.799 AC: 47473 AN: 59388

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

African (AFR) AF: 0.853 AC: 35436 AN: 41522

American (AMR) AF: 0.827 AC: 12630 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2749 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5161 AN: 5178

South Asian (SAS) AF: 0.871 AC: 4200 AN: 4824

European-Finnish (FIN) AF: 0.869 AC: 9210 AN: 10596

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52450 AN: 68018

Other (OTH) AF: 0.810 AC: 1714 AN: 2116

Alfa AF: 0.787 Hom.: 156351

Bravo AF: 0.816

Asia WGS AF: 0.931 AC: 3233 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	CFAP69-related disorder (1)
-	-	1	not provided (1)
-	-	1	Spermatogenic failure 24 (1)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	5.3e-7	T
MetaSVM	Benign	-0.95	T
PhyloP100		1.6
PROVEAN	Benign	0.23	N
REVEL	Benign	0.088
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.042
gMVP		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1029365;

hg19: chr7-89912301;

COSMIC: COSV60188858;