NM_012337.3:c.639G>C

Variant names:

• chr1-159886639-C-G
• rs2501324
• NM_012337.3:c.639G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012337.3(CFAP45):​c.639G>C​(p.Glu213Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP45 NM_012337.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46
• Publications: 0 publications found

Genes affected

CFAP45 (HGNC:17229): (cilia and flagella associated protein 45) Enables AMP binding activity. Involved in establishment of left/right asymmetry and flagellated sperm motility. Located in 9+2 motile cilium; axoneme; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CFAP45 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 11, autosomal, with male infertility

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000272668 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012337.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP45	NM_012337.3	MANE Select	c.639G>C	p.Glu213Asp	missense	Exon 6 of 12	NP_036469.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP45	ENST00000368099.9	TSL:1 MANE Select	c.639G>C	p.Glu213Asp	missense	Exon 6 of 12	ENSP00000357079.4
	CFAP45	ENST00000426543.6	TSL:1	c.384G>C	p.Glu128Asp	missense	Exon 6 of 12	ENSP00000403044.2
	CFAP45	ENST00000479940.2	TSL:5	c.384G>C	p.Glu128Asp	missense	Exon 7 of 7	ENSP00000478944.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.94	T
PhyloP100		4.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.39		Loss of MoRF binding (P = 0.1235)
MVP		0.65
MPC		0.46
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.79
gMVP		0.57
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs2501324; hg19: chr1-159856429;