3-113416627-C-T

Variant names:

• chr3-113416627-C-T
• NM_001164496.2:c.571G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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: Splicing: ADA: 0.3052
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.77

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]

ENSG00000285943 (HGNC:58084):

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

ACMG classification

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
CFAP44	NM_001164496.2	c.571G>A	p.Val191Ile	missense_variant, splice_region_variant	Exon 6 of 35	ENST00000393845.9	NP_001157968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP44	ENST00000393845.9	c.571G>A	p.Val191Ile	missense_variant, splice_region_variant	Exon 6 of 35	5	NM_001164496.2	ENSP00000377428.2
ENSG00000285943	ENST00000649772.1	n.*889G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 25 of 39			ENSP00000497606.1
ENSG00000285943	ENST00000649772.1	n.*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

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;