rs1131692266

Positions:

• chr10-104225491-G-A
• chr10-104225491-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_025145.7(CFAP43):​c.386C>T​(p.Ser129Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CFAP43 NM_025145.7 missense
• Clinical Significance: Not reported in ClinVar
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP43	NM_025145.7	c.386C>T	p.Ser129Phe	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>T	p.Ser129Phe	missense_variant	3/38	1	NM_025145.7	ENSP00000349568	P1
CFAP43	ENST00000278064.7	c.386C>T	p.Ser129Phe	missense_variant	3/22	1		ENSP00000278064
CFAP43	ENST00000369720.6	c.386C>T	p.Ser129Phe	missense_variant	3/11	1		ENSP00000358734
CFAP43	ENST00000369719.2	c.386C>T	p.Ser129Phe	missense_variant	3/8	2		ENSP00000358733

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74356

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;.;T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Uncertain	0.15	D
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-4.3	D;D;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.91
MutPred		0.50		Loss of disorder (P = 0.0529);.;.;.;
MVP		0.85
MPC		0.63
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.61
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;