dbSNP rs137852862: SUGCT:p.Arg101* (chr7-40188569-C-T) – ACMG Classification: Likely_pathogenic (9 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1PP5

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 benign 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

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

glutaric acidemia type 3
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

SUGCT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

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 VariationId is 1851.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193313.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUGCT	NM_001193313.2	MANE Select	c.301C>T	p.Arg101*	stop_gained	Exon 4 of 14	NP_001180242.2	Q9HAC7-1
SUGCT	NM_001193311.2		c.301C>T	p.Arg101*	stop_gained	Exon 4 of 15	NP_001180240.2	Q9HAC7-3
SUGCT	NM_024728.3		c.301C>T	p.Arg101*	stop_gained	Exon 4 of 15	NP_079004.2	Q9HAC7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUGCT	ENST00000335693.9	TSL:1 MANE Select	c.301C>T	p.Arg101*	stop_gained	Exon 4 of 14	ENSP00000338475.5	Q9HAC7-1
SUGCT	ENST00000628514.3	TSL:1	c.301C>T	p.Arg101*	stop_gained	Exon 4 of 15	ENSP00000486291.2	Q9HAC7-3
SUGCT	ENST00000416370.2	TSL:1	c.301C>T	p.Arg101*	stop_gained	Exon 4 of 13	ENSP00000393032.2	H0Y4N1

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

GnomAD2 exomes

AF:

0.000265

AC:

AN:

233638

AF XY:

0.000245

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 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

African (AFR)

AF:

0.0000307

AC:

AN:

32536

American (AMR)

AF:

0.0000476

AC:

AN:

41976

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25776

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39054

South Asian (SAS)

AF:

0.000736

AC:

AN:

81556

European-Finnish (FIN)

AF:

0.000658

AC:

AN:

53190

Middle Eastern (MID)

AF:

0.000525

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.000179

AC:

198

AN:

1106860

Other (OTH)

AF:

0.000418

AC:

AN:

59848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000204

AC:

AN:

151848

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

41408

American (AMR)

AF:

0.000525

AC:

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000416

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.000382

AC:

AN:

10484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67972

Other (OTH)

AF:

0.00143

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000172

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

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glutaryl-CoA oxidase deficiency (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.60

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.81

PhyloP100

1.6

Vest4

0.46

ClinPred

0.88

GERP RS

4.9

Mutation Taster

=0/200

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over