Genetic Variant CFAP70:p.Thr803Ile (chr10-73291267-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367801.1(CFAP70):c.2408C>T(p.Thr803Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000774 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T803A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

CFAP70
NM_001367801.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.225

Variant links:

Genes affected

CFAP70 (HGNC:30726): (cilia and flagella associated protein 70) Predicted to be involved in cilium assembly and cilium movement. Located in ciliary basal body and sperm flagellum. Part of outer dynein arm. Implicated in spermatogenic failure 41. [provided by Alliance of Genome Resources, Apr 2022]

CFAP70 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0057536364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP70	NM_001367801.1 link	c.2408C>T	p.Thr803Ile	missense_variant	Exon 20 of 28	ENST00000355577.9	NP_001354730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP70	ENST00000355577.9 link	c.2408C>T	p.Thr803Ile	missense_variant	Exon 20 of 28	5	NM_001367801.1	ENSP00000347781.4		A0A087WSW1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000179

AC:

AN:

251472

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000705

AC:

103

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00314

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000145

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000428

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2408C>T (p.T803I) alteration is located in exon 20 (coding exon 19) of the CFAP70 gene. This alteration results from a C to T substitution at nucleotide position 2408, causing the threonine (T) at amino acid position 803 to be replaced by an isoleucine (I). 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

0.096

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.58

T;T;.

M_CAP

Benign

0.0055

MetaRNN

Benign

0.0058

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

N;N;.

REVEL

Benign

0.016

Sift

Benign

0.080

T;T;.

Sift4G

Benign

0.11

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.062

MVP

0.092

MPC

0.35

ClinPred

0.020

GERP RS

-0.83

Varity_R

0.037

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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