chr7-90271630-G-C

Variant names:

• chr7-90271630-G-C
• rs375365663
• NM_001039706.3:c.637G>C

Variant summary

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

The NM_001039706.3(CFAP69):​c.637G>C​(p.Glu213Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CFAP69 NM_001039706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96
• Publications: 2 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=0.33430582).

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.637G>C	p.Glu213Gln	missense	Exon 7 of 23	NP_001034795.2	A5D8W1-1
	CFAP69	NM_001160138.2		c.583G>C	p.Glu195Gln	missense	Exon 7 of 23	NP_001153610.1	A5D8W1-5
	CFAP69	NM_001363438.1		c.637G>C	p.Glu213Gln	missense	Exon 7 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.637G>C	p.Glu213Gln	missense	Exon 7 of 23	ENSP00000373948.4	A5D8W1-1
	CFAP69	ENST00000497910.5	TSL:2	c.583G>C	p.Glu195Gln	missense	Exon 7 of 23	ENSP00000419549.1	A5D8W1-5
	CFAP69	ENST00000949775.1		c.538G>C	p.Glu180Gln	missense	Exon 6 of 22	ENSP00000619834.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249296 AF XY: 0.0000148

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: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461406 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726982

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111686

Other (OTH) AF: 0.0000497 AC: 3 AN: 60366

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.32	T
PhyloP100		5.0
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.19
Sift	Benign	0.056	T
Sift4G	Uncertain	0.051	T
Polyphen		0.99	D
Vest4		0.50
MVP		0.67
MPC		0.31
ClinPred		0.59	D
GERP RS		6.2
PromoterAI		0.0046	Neutral
Varity_R		0.16
gMVP		0.40
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs375365663; hg19: chr7-89900944;