NM_001039706.3:c.316C>G

Variant names:

• chr7-90262016-C-G
• rs544953762
• NM_001039706.3:c.316C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039706.3(CFAP69):​c.316C>G​(p.Arg106Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,603,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R106H) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CFAP69 NM_001039706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048036665).

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.316C>G	p.Arg106Gly	missense	Exon 4 of 23	NP_001034795.2	A5D8W1-1
	CFAP69	NM_001160138.2		c.316C>G	p.Arg106Gly	missense	Exon 4 of 23	NP_001153610.1	A5D8W1-5
	CFAP69	NM_001363438.1		c.316C>G	p.Arg106Gly	missense	Exon 4 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.316C>G	p.Arg106Gly	missense	Exon 4 of 23	ENSP00000373948.4	A5D8W1-1
	CFAP69	ENST00000497910.5	TSL:2	c.316C>G	p.Arg106Gly	missense	Exon 4 of 23	ENSP00000419549.1	A5D8W1-5
	CFAP69	ENST00000949775.1		c.316C>G	p.Arg106Gly	missense	Exon 4 of 22	ENSP00000619834.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152062 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000416 AC: 1 AN: 240586 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000903

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1451042 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 721654

African (AFR) AF: 0.00 AC: 0 AN: 32788

American (AMR) AF: 0.00 AC: 0 AN: 42782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25946

East Asian (EAS) AF: 0.0000510 AC: 2 AN: 39200

South Asian (SAS) AF: 0.00 AC: 0 AN: 83618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107772

Other (OTH) AF: 0.00 AC: 0 AN: 59960

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152062 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74282

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.40
DANN	Benign	0.48
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.23
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.026
Sift	Benign	0.32	T
Sift4G	Benign	0.43	T
Polyphen		0.0040	B
Vest4		0.24
MutPred		0.31		Gain of methylation at K102 (P = 0.0446)
MVP		0.072
MPC		0.092
ClinPred		0.040	T
GERP RS		-1.9
Varity_R		0.070
gMVP		0.096
Mutation Taster		=95/5	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: rs544953762; hg19: chr7-89891330;