Genetic Variant CFAP44:p.Ile321Val (chr3-113406971-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164496.2(CFAP44):c.961A>G(p.Ile321Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

CFAP44
NM_001164496.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00300

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:

ENSG00000285943 (HGNC:58084):

ENSG00000285943 links:

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

CFAP44-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07559696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP44	NM_001164496.2 link	c.961A>G	p.Ile321Val	missense_variant	Exon 8 of 35	ENST00000393845.9	NP_001157968.1	Q96MT7-2Q9NUU0Q9UF55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFAP44	ENST00000393845.9 link	c.961A>G	p.Ile321Val	missense_variant	Exon 8 of 35	5	NM_001164496.2	ENSP00000377428.2	Q96MT7-2
ENSG00000285943	ENST00000649772.1 link	n.*1062A>G		non_coding_transcript_exon_variant	Exon 26 of 39			ENSP00000497606.1
ENSG00000285943	ENST00000649772.1 link	n.*1062A>G		3_prime_UTR_variant	Exon 26 of 39			ENSP00000497606.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251480

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.961A>G (p.I321V) alteration is located in exon 8 (coding exon 7) of the CFAP44 gene. This alteration results from a A to G substitution at nucleotide position 961, causing the isoleucine (I) at amino acid position 321 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.9

DANN

Benign

0.93

DEOGEN2

Benign

0.0061

T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.21

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.27

PROVEAN

Benign

0.57

N;N

REVEL

Benign

0.047

Sift

Benign

0.29

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0

B;.

Vest4

0.10

MVP

0.17

MPC

0.077

ClinPred

0.056

GERP RS

-0.11

Varity_R

0.031

gMVP

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over