NM_174978.3:c.204_205delTA
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_174978.3(C14orf39):c.204_205delTA(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
Publications
1 publications found
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]
C14orf39 Gene-Disease associations (from GenCC):
- premature ovarian failure 18Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
- spermatogenic failure 52Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
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 14-60483718-CTA-C is Pathogenic according to our data. Variant chr14-60483718-CTA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 992822.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_174978.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| C14orf39 | NM_174978.3 | MANE Select | c.204_205delTA | p.His68GlnfsTer2 | frameshift | Exon 4 of 18 | NP_777638.3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| C14orf39 | ENST00000321731.8 | TSL:1 MANE Select | c.204_205delTA | p.His68GlnfsTer2 | frameshift | Exon 4 of 18 | ENSP00000324920.3 | Q8N1H7 | |
| C14orf39 | ENST00000557138.5 | TSL:1 | n.106+1161_106+1162delTA | intron | N/A | ENSP00000450476.1 | G3V257 | ||
| C14orf39 | ENST00000917634.1 | c.204_205delTA | p.His68GlnfsTer2 | frameshift | Exon 4 of 18 | ENSP00000587693.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000414 AC: 1AN: 241674 AF XY: 0.00000765 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
241674
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS 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 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1445038
Hom.:
AF XY:
AC XY:
2
AN XY:
719214
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
32780
American (AMR)
AF:
AC:
0
AN:
42934
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25874
East Asian (EAS)
AF:
AC:
0
AN:
39098
South Asian (SAS)
AF:
AC:
0
AN:
83806
European-Finnish (FIN)
AF:
AC:
0
AN:
53108
Middle Eastern (MID)
AF:
AC:
0
AN:
5720
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1101882
Other (OTH)
AF:
AC:
0
AN:
59836
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Azoospermia (1)
1
-
-
Non-obstructive azoospermia (1)
1
-
-
Premature ovarian failure 18 (1)
1
-
-
Spermatogenic failure 52 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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