rs1553756824

Variant names:

• chr3-113363260-T-TC
• rs1553756824
• NM_001164496.2:c.2818dupG

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001164496.2(CFAP44):​c.2818dupG​(p.Glu940GlyfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP44 NM_001164496.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.10
• Publications: 1 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: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-113363260-T-TC is Pathogenic according to our data. Variant chr3-113363260-T-TC is described in ClinVar as Pathogenic. ClinVar VariationId is 523154.Status of the report is no_assertion_criteria_provided, 0 stars.

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.2818dupG	p.Glu940GlyfsTer19	frameshift	Exon 21 of 35	NP_001157968.1	Q96MT7-2
	CFAP44	NM_018338.3		c.2818dupG	p.Glu940GlyfsTer19	frameshift	Exon 21 of 21	NP_060808.2	Q96MT7-1
	SPICE1-CFAP44	NR_183045.1		n.5552dupG		non_coding_transcript_exon	Exon 35 of 49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.2818dupG	p.Glu940GlyfsTer19	frameshift	Exon 21 of 35	ENSP00000377428.2	Q96MT7-2
	CFAP44	ENST00000295868.6	TSL:1	c.2818dupG	p.Glu940GlyfsTer19	frameshift	Exon 21 of 21	ENSP00000295868.2	Q96MT7-1
	SPICE1-CFAP44	ENST00000649772.1		n.*2837dupG		non_coding_transcript_exon	Exon 39 of 39	ENSP00000497606.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Spermatogenic failure 20 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=17/183	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs1553756824; hg19: chr3-113082107;