chr3-113409125-A-T

Variant names:

• chr3-113409125-A-T
• NM_001164496.2:c.871T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164496.2(CFAP44):​c.871T>A​(p.Ser291Thr) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S291L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CFAP44 NM_001164496.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.431
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14481935).

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.871T>A	p.Ser291Thr	missense	Exon 7 of 35	NP_001157968.1	Q96MT7-2
	CFAP44	NM_018338.3		c.871T>A	p.Ser291Thr	missense	Exon 7 of 21	NP_060808.2	Q96MT7-1
	SPICE1-CFAP44	NR_183046.1		n.4152T>A		non_coding_transcript_exon	Exon 24 of 48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.871T>A	p.Ser291Thr	missense	Exon 7 of 35	ENSP00000377428.2	Q96MT7-2
	CFAP44	ENST00000295868.6	TSL:1	c.871T>A	p.Ser291Thr	missense	Exon 7 of 21	ENSP00000295868.2	Q96MT7-1
	SPICE1-CFAP44	ENST00000649772.1		n.*992-2084T>A		intron	N/A	ENSP00000497606.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.19
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.63
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.43
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Benign	0.053	T
Sift4G	Uncertain	0.033	D
Polyphen		0.56	P
Vest4		0.39
MutPred		0.42		Loss of glycosylation at S291 (P = 0.0474)
MVP		0.067
MPC		0.10
ClinPred		0.20	T
GERP RS		-8.0
Varity_R		0.15
gMVP		0.36
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr3-113127972;