3-113416627-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/23 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
• Publications: 0 publications found

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]

SPICE1-CFAP44 (HGNC:58084):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	NM_001164496.2	MANE Select	c.571G>A	p.Val191Ile	missense splice_region	Exon 6 of 35	NP_001157968.1	Q96MT7-2
	CFAP44	NM_018338.3		c.571G>A	p.Val191Ile	missense splice_region	Exon 6 of 21	NP_060808.2	Q96MT7-1
	SPICE1-CFAP44	NR_183045.1		n.3989G>A		splice_region non_coding_transcript_exon	Exon 24 of 49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.571G>A	p.Val191Ile	missense splice_region	Exon 6 of 35	ENSP00000377428.2	Q96MT7-2
	CFAP44	ENST00000295868.6	TSL:1	c.571G>A	p.Val191Ile	missense splice_region	Exon 6 of 21	ENSP00000295868.2	Q96MT7-1
	SPICE1-CFAP44	ENST00000649772.1		n.*889G>A		splice_region non_coding_transcript_exon	Exon 25 of 39	ENSP00000497606.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.8
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.058
Sift	Benign	0.36	T
Sift4G	Benign	0.36	T
Polyphen		0.18	B
Vest4		0.24
MutPred		0.53		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
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

hg19: chr3-113135474;