chr7-90258119-C-G

Variant names:

• chr7-90258119-C-G
• NM_001039706.3:c.202C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039706.3(CFAP69):​c.202C>G​(p.Leu68Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP69 NM_001039706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35
• Publications: 0 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: 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=0.08041331).

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.202C>G	p.Leu68Val	missense	Exon 3 of 23	NP_001034795.2	A5D8W1-1
	CFAP69	NM_001160138.2		c.202C>G	p.Leu68Val	missense	Exon 3 of 23	NP_001153610.1	A5D8W1-5
	CFAP69	NM_001363438.1		c.202C>G	p.Leu68Val	missense	Exon 3 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.202C>G	p.Leu68Val	missense	Exon 3 of 23	ENSP00000373948.4	A5D8W1-1
	CFAP69	ENST00000497910.5	TSL:2	c.202C>G	p.Leu68Val	missense	Exon 3 of 23	ENSP00000419549.1	A5D8W1-5
	CFAP69	ENST00000949775.1		c.202C>G	p.Leu68Val	missense	Exon 3 of 22	ENSP00000619834.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.026
Sift	Benign	0.45	T
Sift4G	Benign	0.27	T
Polyphen		0.022	B
Vest4		0.38
MutPred		0.58		Gain of methylation at K66 (P = 0.0629)
MVP		0.067
MPC		0.13
ClinPred		0.15	T
GERP RS		2.1
PromoterAI		-0.00030	Neutral
Varity_R		0.067
gMVP		0.16
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr7-89887433;