rs80258277

Variant names:

• chr10-87050580-TAAAAAAAA-T
• rs80258277
• NM_005271.5:c.*1163_*1170delTTTTTTTT

Your query was ambiguous. Multiple possible variants found:

• chr10-87050580-TAAAAAAAA-T
• chr10-87050580-TAAAAAAAA-TAAAA
• chr10-87050580-TAAAAAAAA-TAAAAA
• chr10-87050580-TAAAAAAAA-TAAAAAA
• chr10-87050580-TAAAAAAAA-TAAAAAAA
• chr10-87050580-TAAAAAAAA-TAAAAAAAAA
• chr10-87050580-TAAAAAAAA-TAAAAAAAAAA
• chr10-87050580-TAAAAAAAA-TAAAAAAAAAAA

Variant summary

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

The NM_005271.5(GLUD1):​c.*1163_*1170delTTTTTTTT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00000734 in 136,328 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: 𝑓 0.0000073 (0 hom., cov: 32)
• Consequence: GLUD1 NM_005271.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.51
• Publications: 0 publications found

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: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLUD1	NM_005271.5	MANE Select	c.*1163_*1170delTTTTTTTT		3_prime_UTR	Exon 13 of 13	NP_005262.1	P00367-1
	GLUD1	NM_001318900.1		c.*1163_*1170delTTTTTTTT		3_prime_UTR	Exon 13 of 13	NP_001305829.1	P00367-3
	GLUD1	NM_001318901.1		c.*1163_*1170delTTTTTTTT		3_prime_UTR	Exon 16 of 16	NP_001305830.1	P00367-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLUD1	ENST00000277865.5	TSL:1 MANE Select	c.*1163_*1170delTTTTTTTT		3_prime_UTR	Exon 13 of 13	ENSP00000277865.4	P00367-1
	GLUD1	ENST00000682507.1		c.*1163_*1170delTTTTTTTT		splice_region	Exon 13 of 13	ENSP00000508098.1	P00367-2
	GLUD1	ENST00000915201.1		c.*1163_*1170delTTTTTTTT		3_prime_UTR	Exon 13 of 13	ENSP00000585260.1

Frequencies

GnomAD3 genomes AF: 0.00000734 AC: 1 AN: 136328 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000734 AC: 1 AN: 136328 Hom.: 0 Cov.: 32 AF XY: 0.0000152 AC XY: 1 AN XY: 65914

African (AFR) AF: 0.0000270 AC: 1 AN: 37090

American (AMR) AF: 0.00 AC: 0 AN: 13588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3246

East Asian (EAS) AF: 0.00 AC: 0 AN: 4768

South Asian (SAS) AF: 0.00 AC: 0 AN: 4304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62392

Other (OTH) AF: 0.00 AC: 0 AN: 1830

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5

Splicing

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

Other links and lift over

dbSNP: rs80258277; hg19: chr10-88810337;