GeneBe

rs35186250

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005271.5(GLUD1):​c.1403-45_1403-40delTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000336 in 595,246 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

GLUD1
NM_005271.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

Publications

1 publications found
Variant links:
Genes affected
GLUD1 (HGNC:4335): (glutamate dehydrogenase 1) This gene encodes glutamate dehydrogenase, which is a mitochondrial matrix enzyme that catalyzes the oxidative deamination of glutamate to alpha-ketoglutarate and ammonia. This enzyme has an important role in regulating amino acid-induced insulin secretion. It is allosterically activated by ADP and inhibited by GTP and ATP. Activating mutations in this gene are a common cause of congenital hyperinsulinism. Alternative splicing of this gene results in multiple transcript variants. The related glutamate dehydrogenase 2 gene on the human X-chromosome originated from this gene via retrotransposition and encodes a soluble form of glutamate dehydrogenase. Related pseudogenes have been identified on chromosomes 10, 18 and X. [provided by RefSeq, Jan 2016]
GLUD1 Gene-Disease associations (from GenCC):
  • hyperinsulinism-hyperammonemia syndrome
    Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GLUD1NM_005271.5 linkc.1403-45_1403-40delTTTTTT intron_variant Intron 10 of 12 ENST00000277865.5 NP_005262.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GLUD1ENST00000277865.5 linkc.1403-45_1403-40delTTTTTT intron_variant Intron 10 of 12 1 NM_005271.5 ENSP00000277865.4

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.00000336
AC:
2
AN:
595246
Hom.:
0
AF XY:
0.00000310
AC XY:
1
AN XY:
322802
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
15418
American (AMR)
AF:
0.00
AC:
0
AN:
32956
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18530
East Asian (EAS)
AF:
0.00
AC:
0
AN:
31880
South Asian (SAS)
AF:
0.00
AC:
0
AN:
61848
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
37162
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2492
European-Non Finnish (NFE)
AF:
0.00000274
AC:
1
AN:
364562
Other (OTH)
AF:
0.0000329
AC:
1
AN:
30398
⚠️ 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: 0.225
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs35186250; hg19: chr10-88817578; API