rs1262272674

Variant names:

• chr3-113344603-G-A
• rs1262272674
• NM_001164496.2:c.3175C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-113344603-G-A
• chr3-113344603-G-C

Variant summary

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

The NM_001164496.2(CFAP44):​c.3175C>T​(p.Arg1059*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000794 in 1,384,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: CFAP44 NM_001164496.2 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.160
• 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 3-113344603-G-A is Pathogenic according to our data. Variant chr3-113344603-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 523153.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.3175C>T	p.Arg1059*	stop_gained	Exon 23 of 35	NP_001157968.1	Q96MT7-2
	SPICE1-CFAP44	NR_183046.1		n.5989C>T		non_coding_transcript_exon	Exon 37 of 48
	SPICE1-CFAP44	NR_183049.1		n.6104C>T		non_coding_transcript_exon	Exon 41 of 52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.3175C>T	p.Arg1059*	stop_gained	Exon 23 of 35	ENSP00000377428.2	Q96MT7-2
	CFAP44	ENST00000490481.1	TSL:5	n.297-2685C>T		intron	N/A	ENSP00000419269.1	H7C591

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000794 AC: 11 AN: 1384778 Hom.: 0 Cov.: 31 AF XY: 0.00000732 AC XY: 5 AN XY: 683298

African (AFR) AF: 0.00 AC: 0 AN: 31584

American (AMR) AF: 0.00 AC: 0 AN: 35674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35716

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000834 AC: 9 AN: 1078818

Other (OTH) AF: 0.0000173 AC: 1 AN: 57908

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Uncertain	0.21
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.028	N
PhyloP100		0.16
Vest4		0.051
ClinPred		0.70	D
GERP RS		1.9
Mutation Taster		=57/143	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1262272674; hg19: chr3-113063450;