3-113326478-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001164496.2(CFAP44):c.4483C>T(p.Arg1495Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00446 in 1,515,284 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 33 hom. )

Consequence

CFAP44
NM_001164496.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.82

Publications

7 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041759014).

BP6

Variant 3-113326478-G-A is Benign according to our data. Variant chr3-113326478-G-A is described in ClinVar as Benign. ClinVar VariationId is 791437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00868 (1321/152174) while in subpopulation AFR AF = 0.0214 (890/41550). AF 95% confidence interval is 0.0203. There are 16 homozygotes in GnomAd4. There are 644 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

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.4483C>T	p.Arg1495Trp	missense	Exon 28 of 35	NP_001157968.1	Q96MT7-2
SPICE1-CFAP44	NR_183045.1		n.7020C>T		non_coding_transcript_exon	Exon 41 of 49
SPICE1-CFAP44	NR_183046.1		n.7119C>T		non_coding_transcript_exon	Exon 41 of 48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.4483C>T	p.Arg1495Trp	missense	Exon 28 of 35	ENSP00000377428.2	Q96MT7-2
	CFAP44	ENST00000461734.1	TSL:2	n.343C>T		non_coding_transcript_exon	Exon 2 of 10	ENSP00000418795.1	H0Y896

Frequencies

GnomAD3 genomes

AF:

0.00866

AC:

1317

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00662

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000944

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00416

Gnomad OTH

AF:

0.00814

GnomAD2 exomes

AF:

0.00405

AC:

515

AN:

127092

AF XY:

0.00370

show subpopulations

Gnomad AFR exome

AF:

0.0214

Gnomad AMR exome

AF:

0.00339

Gnomad ASJ exome

AF:

0.00274

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00103

Gnomad NFE exome

AF:

0.00408

Gnomad OTH exome

AF:

0.00411

GnomAD4 exome

AF:

0.00399

AC:

5435

AN:

1363110

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

2632

AN XY:

671636

show subpopulations

African (AFR)

AF:

0.0236

AC:

709

AN:

30032

American (AMR)

AF:

0.00328

AC:

100

AN:

30478

Ashkenazi Jewish (ASJ)

AF:

0.00238

AC:

AN:

24390

East Asian (EAS)

AF:

0.000170

AC:

AN:

35268

South Asian (SAS)

AF:

0.00130

AC:

AN:

73210

European-Finnish (FIN)

AF:

0.00183

AC:

AN:

34914

Middle Eastern (MID)

AF:

0.0118

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.00378

AC:

4048

AN:

1072096

Other (OTH)

AF:

0.00506

AC:

289

AN:

57122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

261

522

784

1045

1306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

158

316

474

632

790

<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

AF:

0.00868

AC:

1321

AN:

152174

Hom.:

Cov.:

AF XY:

0.00866

AC XY:

644

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0214

AC:

890

AN:

41550

American (AMR)

AF:

0.00661

AC:

101

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00145

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.000944

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00416

AC:

283

AN:

67968

Other (OTH)

AF:

0.00758

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

148

223

297

371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00596

Hom.:

Bravo

AF:

0.00989

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.0231

AC:

ESP6500EA

AF:

0.00377

AC:

ExAC

AF:

0.00459

AC:

108

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

Eigen

Benign

0.019

Eigen_PC

Benign

-0.024

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.83

PhyloP100

1.8

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.17

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Vest4

0.22

MVP

0.42

MPC

0.25

ClinPred

0.025

GERP RS

4.3

Varity_R

0.29

gMVP

0.24

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over