7-90258128-G-C

Position:

• chr7-90258128-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039706.3(CFAP69):​c.211G>C​(p.Val71Leu) 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. 13/19 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: 1.34

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07964817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP69	NM_001039706.3	c.211G>C	p.Val71Leu	missense_variant	3/23	ENST00000389297.8	NP_001034795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP69	ENST00000389297.8	c.211G>C	p.Val71Leu	missense_variant	3/23	1	NM_001039706.3	ENSP00000373948.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2021

The c.211G>C (p.V71L) alteration is located in exon 3 (coding exon 3) of the CFAP69 gene. This alteration results from a G to C substitution at nucleotide position 211, causing the valine (V) at amino acid position 71 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.76
DEOGEN2	Benign	0.0063	T;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.080	T;T;T
MetaSVM	Benign	-0.96	T
PROVEAN	Benign	0.32	N;N;N
REVEL	Benign	0.057
Sift	Benign	0.94	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.093	B;B;.
Vest4		0.28
MutPred		0.40		Loss of methylation at K72 (P = 0.0391);Loss of methylation at K72 (P = 0.0391);.;
MVP		0.040
MPC		0.064
ClinPred		0.042	T
GERP RS		2.2
Varity_R		0.035
gMVP		0.17

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-89887442;