10-87060835-A-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005271.5(GLUD1):c.1060-10T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,614,148 control chromosomes in the GnomAD database, including 2,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 122 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1897 hom. )

Consequence

GLUD1
NM_005271.5 intron

Scores

Splicing: ADA: 0.4035

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.931

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 10-87060835-A-T is Benign according to our data. Variant chr10-87060835-A-T is described in ClinVar as [Benign]. Clinvar id is 129162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLUD1	NM_005271.5 link	c.1060-10T>A		intron_variant	Intron 7 of 12	ENST00000277865.5	NP_005262.1	P00367-1E9KL48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLUD1	ENST00000277865.5 link	c.1060-10T>A		intron_variant	Intron 7 of 12	1	NM_005271.5	ENSP00000277865.4		P00367-1

Frequencies

GnomAD3 genomes

AF:

0.0313

AC:

4762

AN:

152176

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00927

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.0336

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0505

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0299

AC:

7521

AN:

251470

Hom.:

164

AF XY:

0.0296

AC XY:

4027

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00991

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.0272

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.0353

Gnomad NFE exome

AF:

0.0480

Gnomad OTH exome

AF:

0.0264

GnomAD4 exome

AF:

0.0463

AC:

67662

AN:

1461854

Hom.:

1897

Cov.:

AF XY:

0.0447

AC XY:

32539

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00830

Gnomad4 AMR exome

AF:

0.0111

Gnomad4 ASJ exome

AF:

0.0280

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0126

Gnomad4 FIN exome

AF:

0.0345

Gnomad4 NFE exome

AF:

0.0547

Gnomad4 OTH exome

AF:

0.0399

GnomAD4 genome

AF:

0.0313

AC:

4764

AN:

152294

Hom.:

122

Cov.:

AF XY:

0.0300

AC XY:

2232

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00924

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.0271

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0112

Gnomad4 FIN

AF:

0.0336

Gnomad4 NFE

AF:

0.0505

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0368

Hom.:

Bravo

AF:

0.0295

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 04, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hyperinsulinism-hyperammonemia syndrome

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.40

dbscSNV1_RF

Benign

0.57

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.24

Position offset: -10

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over