10-87057821-GAA-G

Position:

• chr10-87057821-GAA-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005271.5(GLUD1):​c.1403-41_1403-40del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 698,746 control chromosomes in the GnomAD database, including 19 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0093 (17 hom., cov: 0)
  • Exomes 𝑓: 0.038 (2 hom.)
• Consequence: GLUD1 NM_005271.5 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLUD1	NM_005271.5	c.1403-41_1403-40del		intron_variant		ENST00000277865.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLUD1	ENST00000277865.5	c.1403-41_1403-40del		intron_variant		1	NM_005271.5	P1

Frequencies

GnomAD3 genomes AF: 0.00930 AC: 1186 AN: 127564 Hom.: 17 Cov.: 0

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00239

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00148

Gnomad SAS AF: 0.000772

Gnomad FIN AF: 0.000720

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000525

Gnomad OTH AF: 0.00473

GnomAD4 exome AF: 0.0383 AC: 21865 AN: 571150 Hom.: 2 AF XY: 0.0368 AC XY: 11396 AN XY: 309416

Gnomad4 AFR exome AF: 0.0920

Gnomad4 AMR exome AF: 0.0611

Gnomad4 ASJ exome AF: 0.0283

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.0196

Gnomad4 FIN exome AF: 0.0413

Gnomad4 NFE exome AF: 0.0317

Gnomad4 OTH exome AF: 0.0413

GnomAD4 genome AF: 0.00932 AC: 1189 AN: 127596 Hom.: 17 Cov.: 0 AF XY: 0.00937 AC XY: 575 AN XY: 61336

Gnomad4 AFR AF: 0.0304

Gnomad4 AMR AF: 0.00238

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00169

Gnomad4 SAS AF: 0.000776

Gnomad4 FIN AF: 0.000720

Gnomad4 NFE AF: 0.000525

Gnomad4 OTH AF: 0.00469

ClinVar

Not reported in ClinVar

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;