Genetic Variant CFAP43:p.Ser129Tyr (chr10-104225491-G-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_025145.7(CFAP43):c.386C>A(p.Ser129Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

CFAP43
NM_025145.7 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.66

Publications

3 publications found

Variant links:

Genes affected

CFAP43 (HGNC:26684): (cilia and flagella associated protein 43) This gene encodes a member of the cilia- and flagella-associated protein family. [provided by RefSeq, Sep 2016]

CFAP43 Gene-Disease associations (from GenCC):

spermatogenic failure 19
Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, Ambry Genetics
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
normal pressure hydrocephalus
Inheritance: AD Classification: LIMITED Submitted by: ClinGen, Ambry Genetics
primary ciliary dyskinesia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

CFAP43 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.825

PP5

Variant 10-104225491-G-T is Pathogenic according to our data. Variant chr10-104225491-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 430935.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP43	NM_025145.7 link	c.386C>A	p.Ser129Tyr	missense_variant	Exon 3 of 38	ENST00000357060.8	NP_079421.5	Q8NDM7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFAP43	ENST00000357060.8 link	c.386C>A	p.Ser129Tyr	missense_variant	Exon 3 of 38	1	NM_025145.7	ENSP00000349568.3	Q8NDM7-1
CFAP43	ENST00000278064.7 link	c.386C>A	p.Ser129Tyr	missense_variant	Exon 3 of 22	1		ENSP00000278064.3	Q5TA04
CFAP43	ENST00000369720.6 link	c.386C>A	p.Ser129Tyr	missense_variant	Exon 3 of 11	1		ENSP00000358734.2	A0A0C4DFU9
CFAP43	ENST00000369719.2 link	c.386C>A	p.Ser129Tyr	missense_variant	Exon 3 of 8	2		ENSP00000358733.2	Q5TA05

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

249638

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Spermatogenic failure 19

Pathogenic:1

Jul 25, 2017

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;T;.;T

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Uncertain

0.092

MetaRNN

Pathogenic

0.82

D;D;D;D

MetaSVM

Uncertain

0.26

PhyloP100

8.7

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-4.5

D;D;D;D

REVEL

Uncertain

0.59

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.89

MutPred

0.49

Gain of catalytic residue at S129 (P = 0.0587);.;.;.;

MVP

0.86

MPC

0.68

ClinPred

1.0

GERP RS

5.3

Varity_R

0.72

gMVP

0.76

Mutation Taster

=4/96

disease causing (ClinVar)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over