NM_001039706.3:c.340_341delAT

Variant names:

• chr7-90262037-GAT-G
• NM_001039706.3:c.340_341delAT

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001039706.3(CFAP69):​c.340_341delAT​(p.Ile114HisfsTer16) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000696 in 1,436,428 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CFAP69 NM_001039706.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.85

Genes affected

CFAP69 (HGNC:26107): (cilia and flagella associated protein 69) Acts upstream of or within sperm axoneme assembly. Located in cytoplasm and sperm midpiece. Implicated in spermatogenic failure 24. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 12 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 7-90262037-GAT-G is Pathogenic according to our data. Variant chr7-90262037-GAT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3256949.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP69	NM_001039706.3	c.340_341delAT	p.Ile114HisfsTer16	frameshift_variant	Exon 4 of 23	ENST00000389297.8	NP_001034795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP69	ENST00000389297.8	c.340_341delAT	p.Ile114HisfsTer16	frameshift_variant	Exon 4 of 23	1	NM_001039706.3	ENSP00000373948.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436428 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 714570

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.09e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Susceptibility to severe COVID-19 Pathogenic:1

Jul 22, 2024

Molecular Medicine Center, Medical University of Sofia

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

Novel (unreported in gnomAD or dbSNP until April 2024) variant found in severely infected COVID-19 Bulgarian patients in a research study. Variant is classified as likely pathogenic according to the ACMG criteria: PM2,PVS1. -

Computational scores

Source: dbNSFP v4.3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-89891351;