Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_001164496.2(CFAP44):c.1769T>A(p.Leu590Gln) 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L590V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

CFAP44
NM_001164496.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.94

Publications

1 publications found

Variant links:

Genes affected

CFAP44 (HGNC:25631): (cilia and flagella associated protein 44) Enables peptidase activity. Involved in sperm axoneme assembly. Acts upstream of or within microtubule cytoskeleton organization. Predicted to be located in cytoplasm; cytoskeleton; and motile cilium. Implicated in spermatogenic failure 20. [provided by Alliance of Genome Resources, Apr 2022]

CFAP44 Gene-Disease associations (from GenCC):

spermatogenic failure 20
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CFAP44 links:

SPICE1-CFAP44 (HGNC:58084):

SPICE1-CFAP44 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

PP5

Variant 3-113396528-A-T is Pathogenic according to our data. Variant chr3-113396528-A-T is described in ClinVar as Pathogenic. ClinVar VariationId is 523151.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164496.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CFAP44	NM_001164496.2	MANE Select	c.1769T>A	p.Leu590Gln	missense	Exon 14 of 35	NP_001157968.1
CFAP44	NM_018338.3		c.1769T>A	p.Leu590Gln	missense	Exon 14 of 21	NP_060808.2
SPICE1-CFAP44	NR_183047.1		n.4939T>A		non_coding_transcript_exon	Exon 31 of 48

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.1769T>A	p.Leu590Gln	missense	Exon 14 of 35	ENSP00000377428.2
CFAP44	ENST00000295868.6	TSL:1	c.1769T>A	p.Leu590Gln	missense	Exon 14 of 21	ENSP00000295868.2
SPICE1-CFAP44	ENST00000649772.1		n.*1870T>A		non_coding_transcript_exon	Exon 32 of 39	ENSP00000497606.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251098

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Spermatogenic failure 20 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

0.59

PhyloP100

7.9

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-4.6

REVEL

Pathogenic

0.89

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.86

MutPred

0.83

Gain of disorder (P = 0.0091)

MVP

0.65

MPC

0.49

ClinPred

0.99

GERP RS

5.4

Varity_R

0.71

gMVP

0.66

Mutation Taster

=21/79

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs762760856

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over