NM_001039706.3:c.763C>A

Variant names:

• chr7-90271861-C-A
• rs1554359569
• NM_001039706.3:c.763C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001039706.3(CFAP69):​c.763C>A​(p.Gln255Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CFAP69 NM_001039706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32148504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP69	NM_001039706.3	c.763C>A	p.Gln255Lys	missense_variant	Exon 8 of 23	ENST00000389297.8	NP_001034795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP69	ENST00000389297.8	c.763C>A	p.Gln255Lys	missense_variant	Exon 8 of 23	1	NM_001039706.3	ENSP00000373948.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456406 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724028

African (AFR) AF: 0.00 AC: 0 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 44206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.00 AC: 0 AN: 85560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108754

Other (OTH) AF: 0.00 AC: 0 AN: 60136

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.55	T
PhyloP100		4.7
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		1.0	D;P;.
Vest4		0.75
MutPred		0.24		Gain of methylation at Q255 (P = 0.0139);.;.;
MVP		0.30
MPC		0.30
ClinPred		0.83	D
GERP RS		5.7
PromoterAI		-0.025	Neutral
Varity_R		0.36
gMVP		0.42
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs1554359569; hg19: chr7-89901175;