rs786205344
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_182977.3(NNT):c.600-1delG variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000091 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NNT
NM_182977.3 splice_acceptor, intron
NM_182977.3 splice_acceptor, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.00
Genes affected
NNT (HGNC:7863): (nicotinamide nucleotide transhydrogenase) This gene encodes an integral protein of the inner mitochondrial membrane. The enzyme couples hydride transfer between NAD(H) and NADP(+) to proton translocation across the inner mitochondrial membrane. Under most physiological conditions, the enzyme uses energy from the mitochondrial proton gradient to produce high concentrations of NADPH. The resulting NADPH is used for biosynthesis and in free radical detoxification. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.026985588 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.1, offset of 6, new splice context is: atttatttttaaattataAGgct. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-43619030-AG-A is Pathogenic according to our data. Variant chr5-43619030-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 35539.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NNT | NM_182977.3 | c.600-1delG | splice_acceptor_variant, intron_variant | Intron 4 of 21 | ENST00000344920.9 | NP_892022.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000911 AC: 12AN: 1317370Hom.: 0 Cov.: 24 AF XY: 0.0000122 AC XY: 8AN XY: 653496
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
12
AN:
1317370
Hom.:
Cov.:
24
AF XY:
AC XY:
8
AN XY:
653496
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Glucocorticoid deficiency 4 Pathogenic:1
May 27, 2012
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
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Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 9
DS_AL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at