3-113416627-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001164496.2(CFAP44):​c.571G>A​(p.Val191Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CFAP44
NM_001164496.2 missense, splice_region

Scores

1
17
Splicing: ADA: 0.3052
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77
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-AS1 (HGNC:41113): (CFAP44 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2807477).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CFAP44NM_001164496.2 linkc.571G>A p.Val191Ile missense_variant, splice_region_variant Exon 6 of 35 ENST00000393845.9 NP_001157968.1 Q96MT7-2Q9NUU0Q9UF55

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CFAP44ENST00000393845.9 linkc.571G>A p.Val191Ile missense_variant, splice_region_variant Exon 6 of 35 5 NM_001164496.2 ENSP00000377428.2 Q96MT7-2
ENSG00000285943ENST00000649772.1 linkn.*889G>A splice_region_variant, non_coding_transcript_exon_variant Exon 25 of 39 ENSP00000497606.1
ENSG00000285943ENST00000649772.1 linkn.*889G>A 3_prime_UTR_variant Exon 25 of 39 ENSP00000497606.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Dec 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.571G>A (p.V191I) 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 571, causing the valine (V) at amino acid position 191 to be replaced by an isoleucine (I). 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
0.073
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.52
CADD
Uncertain
24
DANN
Benign
0.92
DEOGEN2
Benign
0.010
T;.
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.038
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.28
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.62
N;N
REVEL
Benign
0.058
Sift
Benign
0.36
T;T
Sift4G
Benign
0.36
T;T
Polyphen
0.18
B;.
Vest4
0.24
MutPred
0.53
Loss of catalytic residue at V191 (P = 0.0348);Loss of catalytic residue at V191 (P = 0.0348);
MVP
0.20
MPC
0.31
ClinPred
0.56
D
GERP RS
4.0
Varity_R
0.083
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.31
dbscSNV1_RF
Benign
0.53
SpliceAI score (max)
0.090
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.

Other links and lift over

hg19: chr3-113135474; API