rs1131692171
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_015909.4(NBAS):c.586C>T(p.Gln196Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
NBAS
NM_015909.4 stop_gained
NM_015909.4 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 9.65
Genes affected
NBAS (HGNC:15625): (NBAS subunit of NRZ tethering complex) This gene encodes a protein with two leucine zipper domains, a ribosomal protein S14 signature domain and a Sec39 like domain. The protein is thought to be involved in Golgi-to-ER transport. Mutations in this gene are associated with short stature, optic nerve atrophy, and Pelger-Huet anomaly. [provided by RefSeq, Oct 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
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Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-15536479-G-A is Pathogenic according to our data. Variant chr2-15536479-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 430659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NBAS | NM_015909.4 | c.586C>T | p.Gln196Ter | stop_gained | 8/52 | ENST00000281513.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NBAS | ENST00000281513.10 | c.586C>T | p.Gln196Ter | stop_gained | 8/52 | 1 | NM_015909.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151738Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461268Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726966
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151738Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74042
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 29, 2023 | This sequence change creates a premature translational stop signal (p.Gln196*) in the NBAS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NBAS are known to be pathogenic (PMID: 26073778, 26541327, 27789416, 28031453). This variant is present in population databases (no rsID available, gnomAD 0.1%). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 430659). This premature translational stop signal has been observed in individual(s) with recurrent acute liver failure (PMID: 28629372). - |
Short stature-optic atrophy-Pelger-HuC+t anomaly syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital | Jul 11, 2017 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at