Genetic Variant CFAP44:p.Met329Leu (chr3-113406947-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164496.2(CFAP44):c.985A>C(p.Met329Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M329V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CFAP44
NM_001164496.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Publications

0 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 links:

SPICE1-CFAP44 (HGNC:58084):

SPICE1-CFAP44 links:

CFAP44-AS1 (HGNC:41113): (CFAP44 antisense RNA 1)

CFAP44-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08520797).

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	UniProt
CFAP44	NM_001164496.2	MANE Select	c.985A>C	p.Met329Leu	missense	Exon 8 of 35	NP_001157968.1	Q96MT7-2
CFAP44	NM_018338.3		c.985A>C	p.Met329Leu	missense	Exon 8 of 21	NP_060808.2	Q96MT7-1
SPICE1-CFAP44	NR_183045.1		n.4186A>C		non_coding_transcript_exon	Exon 25 of 49

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.985A>C	p.Met329Leu	missense	Exon 8 of 35	ENSP00000377428.2	Q96MT7-2
CFAP44	ENST00000295868.6	TSL:1	c.985A>C	p.Met329Leu	missense	Exon 8 of 21	ENSP00000295868.2	Q96MT7-1
SPICE1-CFAP44	ENST00000649772.1		n.*1086A>C		non_coding_transcript_exon	Exon 26 of 39	ENSP00000497606.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111816

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.69

M_CAP

Benign

0.0052

MetaRNN

Benign

0.085

MetaSVM

Benign

-0.94

PhyloP100

1.2

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.22

REVEL

Benign

0.016

Sift

Benign

0.054

Sift4G

Benign

0.11

Polyphen

0.019

Vest4

0.36

MutPred

0.43

Gain of catalytic residue at M329 (P = 0.0071)

MVP

0.072

MPC

0.21

ClinPred

0.11

GERP RS

2.0

Varity_R

0.11

gMVP

0.27

Mutation Taster

=92/8

polymorphism

(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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over