Variant 7-90258145-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039706.3(CFAP69):c.228G>C(p.Gln76His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,456,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CFAP69
NM_001039706.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.769

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.09724048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP69	NM_001039706.3 linkuse as main transcript	c.228G>C	p.Gln76His	missense_variant	3/23	ENST00000389297.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP69	ENST00000389297.8 linkuse as main transcript	c.228G>C	p.Gln76His	missense_variant	3/23	1	NM_001039706.3	P1	A5D8W1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247504

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134290

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1456908

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724904

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.228G>C (p.Q76H) 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 228, causing the glutamine (Q) at amino acid position 76 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

T;.;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.51

T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.097

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.16

MutPred

0.26

Gain of catalytic residue at Q76 (P = 0.0679);Gain of catalytic residue at Q76 (P = 0.0679);.;

MVP

0.014

MPC

0.062

ClinPred

0.077

GERP RS

2.1

Varity_R

0.057

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over