16-1839351-GAGAA-G
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001163560.3(MEIOB):c.1118_1121delTTCT(p.Phe373SerfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,802 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: 6.8e-7 ( 0 hom. )
Consequence
MEIOB
NM_001163560.3 frameshift
NM_001163560.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.74
Publications
0 publications found
Genes affected
MEIOB (HGNC:28569): (meiosis specific with OB-fold) Predicted to enable chromatin binding activity; single-stranded DNA 3'-5' exodeoxyribonuclease activity; and single-stranded DNA binding activity. Predicted to be involved in double-strand break repair via homologous recombination; fertilization; and meiotic nuclear division. Predicted to be located in cytoplasm. Implicated in spermatogenic failure 22. [provided by Alliance of Genome Resources, Apr 2022]
FAHD1 (HGNC:14169): (fumarylacetoacetate hydrolase domain containing 1) Enables acetylpyruvate hydrolase activity; fumarylpyruvate hydrolase activity; and oxaloacetate decarboxylase activity. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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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 16-1839351-GAGAA-G is Pathogenic according to our data. Variant chr16-1839351-GAGAA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 1328958.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001163560.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| MEIOB | MANE Select | c.1118_1121delTTCT | p.Phe373SerfsTer6 | frameshift | Exon 12 of 14 | NP_001157032.1 | Q8N635-2 | ||
| MEIOB | c.1118_1121delTTCT | p.Phe373SerfsTer6 | frameshift | Exon 12 of 13 | NP_689977.2 | Q8N635-1 | |||
| FAHD1 | c.*102_*105delAAGA | 3_prime_UTR | Exon 3 of 3 | NP_001018114.2 | Q6P587-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MEIOB | TSL:5 MANE Select | c.1118_1121delTTCT | p.Phe373SerfsTer6 | frameshift | Exon 12 of 14 | ENSP00000314484.3 | Q8N635-2 | ||
| FAHD1 | TSL:1 | c.*49_*52delAAGA | 3_prime_UTR | Exon 2 of 2 | ENSP00000372114.5 | Q6P587-2 | |||
| MEIOB | TSL:5 | c.1118_1121delTTCT | p.Phe373SerfsTer6 | frameshift | Exon 12 of 13 | ENSP00000380504.3 | Q8N635-1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461802Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727208 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1461802
Hom.:
AF XY:
AC XY:
0
AN XY:
727208
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:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111940
Other (OTH)
AF:
AC:
1
AN:
60396
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
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0
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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4
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Azoospermia (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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