3-113358865-ACATCAAAATC-A

Variant names:

• chr3-113358865-ACATCAAAATC-A
• rs1553756374
• NM_001164496.2:c.2935_2944delGATTTTGATG

Variant summary

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

The NM_001164496.2(CFAP44):​c.2935_2944delGATTTTGATG​(p.Asp979fs) variant causes a frameshift, splice region change. 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, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.87
• 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 3-113358865-ACATCAAAATC-A is Pathogenic according to our data. Variant chr3-113358865-ACATCAAAATC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 523150.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.2935_2944delGATTTTGATG	p.Asp979fs	frameshift splice_region	Exon 22 of 35	NP_001157968.1	Q96MT7-2
	SPICE1-CFAP44	NR_183045.1		n.5669_5678delGATTTTGATG		splice_region non_coding_transcript_exon	Exon 36 of 49
	SPICE1-CFAP44	NR_183046.1		n.5749_5758delGATTTTGATG		splice_region non_coding_transcript_exon	Exon 36 of 48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.2935_2944delGATTTTGATG	p.Asp979fs	frameshift splice_region	Exon 22 of 35	ENSP00000377428.2	Q96MT7-2
	CFAP44	ENST00000490481.1	TSL:5	n.166_175delGATTTTGATG		splice_region non_coding_transcript_exon	Exon 2 of 4	ENSP00000419269.1	H7C591

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

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		5.9
Mutation Taster		=24/176	disease causing (ClinVar)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1553756374; hg19: chr3-113077712;