Genetic Variant GLUD1:c.1403-40_1403-39insTTGTTTTCTATTTTTTTATTTTTTTTTTTTTTTTTTTTTTT (chr10-87057821-G-GAAAAAAAAAAAAAAAAAAAAAAATAAAAAAATAGAAAACAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_005271.5(GLUD1):c.1403-40_1403-39insTTGTTTTCTATTTTTTTATTTTTTTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

GLUD1
NM_005271.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.237

Publications

0 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

GLUD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005271.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GLUD1	NM_005271.5	MANE Select	c.1403-40_1403-39insTTGTTTTCTATTTTTTTATTTTTTTTTTTTTTTTTTTTTTT	intron	N/A	NP_005262.1
GLUD1	NM_001318900.1		c.1004-40_1004-39insTTGTTTTCTATTTTTTTATTTTTTTTTTTTTTTTTTTTTTT	intron	N/A	NP_001305829.1
GLUD1	NM_001318901.1		c.902-40_902-39insTTGTTTTCTATTTTTTTATTTTTTTTTTTTTTTTTTTTTTT	intron	N/A	NP_001305830.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GLUD1	ENST00000277865.5	TSL:1 MANE Select	c.1403-40_1403-39insTTGTTTTCTATTTTTTTATTTTTTTTTTTTTTTTTTTTTTT	intron	N/A	ENSP00000277865.4
GLUD1	ENST00000684338.1		c.1403-40_1403-39insTTGTTTTCTATTTTTTTATTTTTTTTTTTTTTTTTTTTTTT	intron	N/A	ENSP00000507457.1
GLUD1	ENST00000684201.1		c.1127-40_1127-39insTTGTTTTCTATTTTTTTATTTTTTTTTTTTTTTTTTTTTTT	intron	N/A	ENSP00000507887.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000168

AC:

AN:

595256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

322804

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:

AN:

15418

American (AMR)

AF:

0.00

AC:

AN:

32956

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18532

East Asian (EAS)

AF:

0.00

AC:

AN:

31880

South Asian (SAS)

AF:

0.00

AC:

AN:

61848

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2492

European-Non Finnish (NFE)

AF:

0.00000274

AC:

AN:

364570

Other (OTH)

AF:

0.00

AC:

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

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.24

Splicing

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

Publications

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10-87057821-GAAAAAA-GAAAAAAAAAAAAAAAAAAAAAAATAAAAAAATAGAAAACAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over