10-104225491-G-T

Position:

• chr10-104225491-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.66

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 430935.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP43	NM_025145.7	c.386C>A	p.Ser129Tyr	missense_variant	3/38	ENST00000357060.8	NP_079421.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP43	ENST00000357060.8	c.386C>A	p.Ser129Tyr	missense_variant	3/38	1	NM_025145.7	ENSP00000349568.3
CFAP43	ENST00000278064.7	c.386C>A	p.Ser129Tyr	missense_variant	3/22	1		ENSP00000278064.3
CFAP43	ENST00000369720.6	c.386C>A	p.Ser129Tyr	missense_variant	3/11	1		ENSP00000358734.2
CFAP43	ENST00000369719.2	c.386C>A	p.Ser129Tyr	missense_variant	3/8	2		ENSP00000358733.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 19 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	29
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	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Uncertain	0.092	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Uncertain	0.26	D
PrimateAI	Uncertain	0.66	T
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	D
GERP RS		5.3
Varity_R		0.72
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs1131692266; hg19: chr10-105985249;