rs1060218

Positions:

chr19-12897793-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000159.4(GCDH):c.1173G>T(p.Gly391=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,612,912 control chromosomes in the GnomAD database, including 103,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7709 hom., cov: 30)

Exomes 𝑓: 0.36 ( 95825 hom. )

Consequence

GCDH
NM_000159.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.11

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 19-12897793-G-T is Benign according to our data. Variant chr19-12897793-G-T is described in ClinVar as [Benign]. Clinvar id is 92529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-12897793-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GCDH	NM_000159.4 linkuse as main transcript	c.1173G>T	p.Gly391=	synonymous_variant	11/12	ENST00000222214.10	NP_000150.1
GCDH	NM_013976.5 linkuse as main transcript	c.1173G>T	p.Gly391=	synonymous_variant	11/12		NP_039663.1
GCDH	NR_102316.1 linkuse as main transcript	n.1336G>T		non_coding_transcript_exon_variant	11/12
GCDH	NR_102317.1 linkuse as main transcript	n.1554G>T		non_coding_transcript_exon_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCDH	ENST00000222214.10 linkuse as main transcript	c.1173G>T	p.Gly391=	synonymous_variant	11/12	1	NM_000159.4	ENSP00000222214	P1	Q92947-1

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46581

AN:

151716

Hom.:

7691

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.317

GnomAD3 exomes

AF:

0.330

AC:

83034

AN:

251404

Hom.:

14792

AF XY:

0.328

AC XY:

44535

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.199

Gnomad AMR exome

AF:

0.447

Gnomad ASJ exome

AF:

0.286

Gnomad EAS exome

AF:

0.139

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.355

AC:

519119

AN:

1461078

Hom.:

95825

Cov.:

AF XY:

0.352

AC XY:

255790

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.189

Gnomad4 AMR exome

AF:

0.441

Gnomad4 ASJ exome

AF:

0.283

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.307

Gnomad4 NFE exome

AF:

0.377

Gnomad4 OTH exome

AF:

0.334

GnomAD4 genome

AF:

0.307

AC:

46632

AN:

151834

Hom.:

7709

Cov.:

AF XY:

0.303

AC XY:

22507

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.284

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.264

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.322

Alfa

AF:

0.352

Hom.:

12125

Bravo

AF:

0.313

Asia WGS

AF:

0.250

AC:

870

AN:

3478

EpiCase

AF:

0.369

EpiControl

AF:

0.368

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glutaric aciduria, type 1

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 13, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 16, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Elevated circulating glutaric acid concentration

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.77

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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