Variant 7-40188569-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_001193313.2(SUGCT):c.301C>T(p.Arg101*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,598,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

SUGCT
NM_001193313.2 stop_gained

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:2U:1

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

SUGCT (HGNC:16001): (succinyl-CoA:glutarate-CoA transferase) This gene encodes a protein that is similar to members of the CaiB/baiF CoA-transferase protein family. Mutations in this gene are associated with glutaric aciduria type III. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

SUGCT links:

SUGCT (HGNC:):

SUGCT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 7-40188569-C-T is Pathogenic according to our data. Variant chr7-40188569-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1851.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Likely_pathogenic=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUGCT	NM_001193313.2 linkuse as main transcript	c.301C>T	p.Arg101*	stop_gained	4/14	ENST00000335693.9	NP_001180242.2	Q9HAC7B4DJF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUGCT	ENST00000335693.9 linkuse as main transcript	c.301C>T	p.Arg101*	stop_gained	4/14	1	NM_001193313.2	ENSP00000338475.5		Q9HAC7

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

151734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000526

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.000382

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.000265

AC:

AN:

233638

Hom.:

AF XY:

0.000245

AC XY:

AN XY:

126536

show subpopulations

Gnomad AFR exome

AF:

0.0000689

Gnomad AMR exome

AF:

0.0000643

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.000119

Gnomad SAS exome

AF:

0.000722

Gnomad FIN exome

AF:

0.000800

Gnomad NFE exome

AF:

0.000157

Gnomad OTH exome

AF:

0.000528

GnomAD4 exome

AF:

0.000225

AC:

325

AN:

1446508

Hom.:

Cov.:

AF XY:

0.000198

AC XY:

142

AN XY:

718668

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.0000476

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.000736

Gnomad4 FIN exome

AF:

0.000658

Gnomad4 NFE exome

AF:

0.000179

Gnomad4 OTH exome

AF:

0.000418

GnomAD4 genome

AF:

0.000204

AC:

AN:

151848

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000525

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.000382

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000145

Hom.:

Bravo

AF:

0.000223

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000273

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.000265

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:2Uncertain:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Glutaryl-CoA oxidase deficiency

Pathogenic:2Uncertain:1

Likely pathogenic, criteria provided, single submitter	clinical testing	Neuberg Centre For Genomic Medicine, NCGM	-	The stop-gained variant c.301C>T p.Arg101Ter in the SUGCT gene has been reported in an individual in homozygous state affected with Glutaric Aciduria, Type 3 Niska-Blakie et al., 2020; Sherman et al., 2008. The variant has 0.02% allele frequency in gnomAD Exomes and is novel not in any individuals in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain significance/ Pathogenic. However, study on multiple affected individuals and functional studies on the pathogenicity of the variant is unavailable. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants has been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. -
Pathogenic, no assertion criteria provided	literature only	OMIM	Nov 01, 2008	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genomic Research Center, Shahid Beheshti University of Medical Sciences	Apr 27, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.60

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.81

Vest4

0.46

ClinPred

0.88

GERP RS

4.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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