chr14-60465993-C-A
Position:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_174978.3(C14orf39):c.958G>T(p.Glu320Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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)
Consequence
C14orf39
NM_174978.3 stop_gained
NM_174978.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 1.68
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]
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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 14-60465993-C-A is Pathogenic according to our data. Variant chr14-60465993-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 992823.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-60465993-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C14orf39 | NM_174978.3 | c.958G>T | p.Glu320Ter | stop_gained | 11/18 | ENST00000321731.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C14orf39 | ENST00000321731.8 | c.958G>T | p.Glu320Ter | stop_gained | 11/18 | 1 | NM_174978.3 | P1 | |
C14orf39 | ENST00000557138.5 | c.*272G>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/13 | 1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 27
GnomAD4 exome
Cov.:
27
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
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 | - - |
Non-obstructive azoospermia Pathogenic:1
Pathogenic, no assertion criteria provided | research | Molecular and Cell Genetics Laboratory, University of Science and Technology of China | Feb 10, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -14
Find out detailed SpliceAI scores and Pangolin per-transcript scores at