chr19-12891219-AGC-GG

Variant names:

• chr19-12891219-AGC-GG
• rs1555748835
• ENST00000591470.5:c.-86_-84delAGCinsGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000591470.5(GCDH):​c.-86_-84delAGCinsGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GCDH ENST00000591470.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.318
• Publications: 0 publications found

Genes affected

GCDH (HGNC:4189): (glutaryl-CoA dehydrogenase) The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family. It catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. The enzyme exists in the mitochondrial matrix as a homotetramer of 45-kD subunits. Mutations in this gene result in the metabolic disorder glutaric aciduria type 1, which is also known as glutaric acidemia type I. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 12. [provided by RefSeq, Mar 2013]

GCDH Gene-Disease associations (from GenCC):

• glutaryl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Myriad Women’s Health, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-12891219-AGC-GG is Benign according to our data. Variant chr19-12891219-AGC-GG is described in ClinVar as Likely_benign. ClinVar VariationId is 508017.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000591470.5. 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
	GCDH	NM_000159.4	MANE Select	c.-35+17_-35+19delAGCinsGG		intron	N/A	NP_000150.1	Q92947-1
	GCDH	NM_013976.5		c.-35+17_-35+19delAGCinsGG		intron	N/A	NP_039663.1	Q92947-2
	GCDH	NR_102316.1		n.74+17_74+19delAGCinsGG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCDH	ENST00000591470.5	TSL:1	c.-86_-84delAGCinsGG		5_prime_UTR	Exon 1 of 11	ENSP00000466845.1	Q92947-1
	GCDH	ENST00000222214.10	TSL:1 MANE Select	c.-35+17_-35+19delAGCinsGG		intron	N/A	ENSP00000222214.4	Q92947-1
	GCDH	ENST00000590627.5	TSL:1	n.23+17_23+19delAGCinsGG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32

Splicing

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

Other links and lift over

dbSNP: rs1555748835; hg19: chr19-13002033;