chr14-60483718-CTA-C
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_174978.3(C14orf39):c.204_205del(p.His68GlnfsTer2) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000138 in 1,445,038 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000014 ( 0 hom. )
Consequence
C14orf39
NM_174978.3 frameshift
NM_174978.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.72
Genes affected
C14orf39 (HGNC:19849): (chromosome 14 open reading frame 39) Predicted to be involved in gamete generation and meiosis I. Predicted to be located in chromosome. Predicted to be active in central element. Implicated in primary ovarian insufficiency 18 and spermatogenic failure 52. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 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 14-60483718-CTA-C is Pathogenic according to our data. Variant chr14-60483718-CTA-C is described in ClinVar as [Pathogenic]. Clinvar id is 992822.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-60483718-CTA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C14orf39 | NM_174978.3 | c.204_205del | p.His68GlnfsTer2 | frameshift_variant | 4/18 | ENST00000321731.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C14orf39 | ENST00000321731.8 | c.204_205del | p.His68GlnfsTer2 | frameshift_variant | 4/18 | 1 | NM_174978.3 | P1 | |
C14orf39 | ENST00000557138.5 | c.106+1161_106+1162del | intron_variant, NMD_transcript_variant | 1 | |||||
C14orf39 | ENST00000555476.5 | c.117_118del | p.His39GlnfsTer2 | frameshift_variant | 3/5 | 5 | |||
C14orf39 | ENST00000556799.1 | c.204_205del | p.His68GlnfsTer2 | frameshift_variant | 5/6 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000414 AC: 1AN: 241674Hom.: 0 AF XY: 0.00000765 AC XY: 1AN XY: 130734
GnomAD3 exomes
AF:
AC:
1
AN:
241674
Hom.:
AF XY:
AC XY:
1
AN XY:
130734
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1445038Hom.: 0 AF XY: 0.00000278 AC XY: 2AN XY: 719214
GnomAD4 exome
AF:
AC:
2
AN:
1445038
Hom.:
AF XY:
AC XY:
2
AN XY:
719214
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Spermatogenic failure 52 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 23, 2021 | - - |
Premature ovarian failure 18 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 23, 2021 | - - |
Non-obstructive azoospermia Pathogenic:1
Pathogenic, no assertion criteria provided | research | Molecular and Cell Genetics Laboratory, University of Science and Technology of China | Nov 14, 2018 | - - |
Azoospermia Pathogenic:1
Pathogenic, no assertion criteria provided | case-control | Genetics of Infertility and Preimplantation Genetic Diagnosis, Centre Hospitalier Universitaire Grenoble Alpes | Dec 20, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at