Genetic Variant CFAP44:p.Ser205Asn (chr3-113416584-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001164496.2(CFAP44):c.614G>A(p.Ser205Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,460,258 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: not found (cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

CFAP44
NM_001164496.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.120

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048070014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP44	NM_001164496.2 link	c.614G>A	p.Ser205Asn	missense_variant	Exon 6 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.614G>A	p.Ser205Asn	missense_variant	Exon 6 of 35	5	NM_001164496.2	ENSP00000377428.2	Q96MT7-2
ENSG00000285943	ENST00000649772.1 link	n.*932G>A		non_coding_transcript_exon_variant	Exon 25 of 39			ENSP00000497606.1
ENSG00000285943	ENST00000649772.1 link	n.*932G>A		3_prime_UTR_variant	Exon 25 of 39			ENSP00000497606.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000431

AC:

AN:

1460258

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

726460

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000558

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Mar 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.614G>A (p.S205N) alteration is located in exon 6 (coding exon 5) of the CFAP44 gene. This alteration results from a G to A substitution at nucleotide position 614, causing the serine (S) at amino acid position 205 to be replaced by an asparagine (N). 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

0.074

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.1

DANN

Benign

0.79

DEOGEN2

Benign

0.0064

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.42

N;N

REVEL

Benign

0.032

Sift

Benign

0.47

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.0040

B;.

Vest4

0.18

MutPred

0.39

Loss of ubiquitination at K203 (P = 0.0683);Loss of ubiquitination at K203 (P = 0.0683);

MVP

0.040

MPC

0.12

ClinPred

0.028

GERP RS

-1.8

Varity_R

0.044

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over