Genetic Variant NM_001164496.2:c.5273T>C (chr3-113294787-A-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.5273T>C(p.Met1758Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000275 in 1,383,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

CFAP44
NM_001164496.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

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 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:

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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=0.18399414).

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.5273T>C	p.Met1758Thr	missense	Exon 34 of 35	NP_001157968.1	Q96MT7-2
SPICE1-CFAP44	NR_183045.1		n.7907T>C		non_coding_transcript_exon	Exon 48 of 49
SPICE1-CFAP44	NR_183046.1		n.7909T>C		non_coding_transcript_exon	Exon 47 of 48

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.5273T>C	p.Met1758Thr	missense	Exon 34 of 35	ENSP00000377428.2	Q96MT7-2
CFAP44	ENST00000461734.1	TSL:2	n.1133T>C		non_coding_transcript_exon	Exon 8 of 10	ENSP00000418795.1	H0Y896
CFAP44	ENST00000465510.1	TSL:4	n.558T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000210

AC:

AN:

143072

AF XY:

0.0000131

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000416

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000339

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000275

AC:

AN:

1383654

Hom.:

Cov.:

AF XY:

0.0000322

AC XY:

AN XY:

682754

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31502

American (AMR)

AF:

0.0000282

AC:

AN:

35490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25154

East Asian (EAS)

AF:

0.00

AC:

AN:

35632

South Asian (SAS)

AF:

0.00

AC:

AN:

78896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

1078390

Other (OTH)

AF:

0.0000518

AC:

AN:

57902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

0.012

Eigen_PC

Benign

0.033

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.48

M_CAP

Benign

0.0084

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

PhyloP100

1.4

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.5

REVEL

Benign

0.14

Sift

Benign

0.38

Sift4G

Benign

0.51

Vest4

0.37

MVP

0.48

MPC

0.11

ClinPred

0.49

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.067

gMVP

0.32

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over