10-87057821-GAAAAAA-GAAAAA

Position:

• chr10-87057821-GAAAAAA-GAAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005271.5(GLUD1):​c.1403-40del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (9709 hom., cov: 0)
  • Exomes 𝑓: 0.33 (486 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLUD1 NM_005271.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.237

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-87057821-GA-G is Benign according to our data. Variant chr10-87057821-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 435339.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLUD1	NM_005271.5	c.1403-40del		intron_variant		ENST00000277865.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLUD1	ENST00000277865.5	c.1403-40del		intron_variant		1	NM_005271.5	P1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 49775 AN: 127460 Hom.: 9695 Cov.: 0

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.221

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.382

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.335 AC: 186534 AN: 557504 Hom.: 486 Cov.: 0 AF XY: 0.332 AC XY: 99756 AN XY: 300520

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.391 AC: 49820 AN: 127492 Hom.: 9709 Cov.: 0 AF XY: 0.397 AC XY: 24342 AN XY: 61298

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.385

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 29, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs35186250; hg19: chr10-88817578;