10-104225491-G-C

Variant names:

• chr10-104225491-G-C
• NM_025145.7:c.386C>G

Variant summary

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

The NM_025145.7(CFAP43):​c.386C>G​(p.Ser129Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,382 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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, 0.791

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP43	NM_025145.7	c.386C>G	p.Ser129Cys	missense_variant	Exon 3 of 38	ENST00000357060.8	NP_079421.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP43	ENST00000357060.8	c.386C>G	p.Ser129Cys	missense_variant	Exon 3 of 38	1	NM_025145.7	ENSP00000349568.3
CFAP43	ENST00000278064.7	c.386C>G	p.Ser129Cys	missense_variant	Exon 3 of 22	1		ENSP00000278064.3
CFAP43	ENST00000369720.6	c.386C>G	p.Ser129Cys	missense_variant	Exon 3 of 11	1		ENSP00000358734.2
CFAP43	ENST00000369719.2	c.386C>G	p.Ser129Cys	missense_variant	Exon 3 of 8	2		ENSP00000358733.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460382 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726490

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T;.;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.79	D;D;D;D
MetaSVM	Uncertain	0.19	D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.79
MutPred		0.53		Gain of catalytic residue at S129 (P = 0.0087);.;.;.;
MVP		0.85
MPC		0.59
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.41
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-105985249;