rs763717583

Variant names:

• chr3-113294787-A-G
• rs763717583
• NM_001164496.2:c.5273T>C

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.5273T>C​(p.Met1758Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000275 in 1,383,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: CFAP44 NM_001164496.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41
• 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]

CFAP44 Gene-Disease associations (from GenCC):

• spermatogenic failure 20

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SPICE1-CFAP44 (HGNC:58084):

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=0.18399414).

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.5273T>C	p.Met1758Thr	missense	Exon 34 of 35	NP_001157968.1	Q96MT7-2
	SPICE1-CFAP44	NR_183045.1		n.7907T>C		non_coding_transcript_exon	Exon 48 of 49
	SPICE1-CFAP44	NR_183046.1		n.7909T>C		non_coding_transcript_exon	Exon 47 of 48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.5273T>C	p.Met1758Thr	missense	Exon 34 of 35	ENSP00000377428.2	Q96MT7-2
	CFAP44	ENST00000461734.1	TSL:2	n.1133T>C		non_coding_transcript_exon	Exon 8 of 10	ENSP00000418795.1	H0Y896
	CFAP44	ENST00000465510.1	TSL:4	n.558T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000210 AC: 3 AN: 143072 AF XY: 0.0000131

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000416

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000339

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000275 AC: 38 AN: 1383654 Hom.: 0 Cov.: 30 AF XY: 0.0000322 AC XY: 22 AN XY: 682754

African (AFR) AF: 0.00 AC: 0 AN: 31502

American (AMR) AF: 0.0000282 AC: 1 AN: 35490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25154

East Asian (EAS) AF: 0.00 AC: 0 AN: 35632

South Asian (SAS) AF: 0.00 AC: 0 AN: 78896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.0000315 AC: 34 AN: 1078390

Other (OTH) AF: 0.0000518 AC: 3 AN: 57902

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.97
Eigen	Benign	0.012
Eigen_PC	Benign	0.033
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.14
Sift	Benign	0.38	T
Sift4G	Benign	0.51	T
Vest4		0.37
MVP		0.48
MPC		0.11
ClinPred		0.49	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.32
Mutation Taster		=87/13	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs763717583; hg19: chr3-113013634;