7-40188569-C-G

Variant names:

• chr7-40188569-C-G
• rs137852862
• NM_001193313.2:c.301C>G
• SUGCT p.Arg101Gly

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001193313.2(SUGCT):​c.301C>G​(p.Arg101Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SUGCT NM_001193313.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.948

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUGCT	NM_001193313.2	MANE Select	c.301C>G	p.Arg101Gly	missense	Exon 4 of 14	NP_001180242.2	Q9HAC7-1
	SUGCT	NM_001193311.2		c.301C>G	p.Arg101Gly	missense	Exon 4 of 15	NP_001180240.2	Q9HAC7-3
	SUGCT	NM_024728.3		c.301C>G	p.Arg101Gly	missense	Exon 4 of 15	NP_079004.2	Q9HAC7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUGCT	ENST00000335693.9	TSL:1 MANE Select	c.301C>G	p.Arg101Gly	missense	Exon 4 of 14	ENSP00000338475.5	Q9HAC7-1
	SUGCT	ENST00000628514.3	TSL:1	c.301C>G	p.Arg101Gly	missense	Exon 4 of 15	ENSP00000486291.2	Q9HAC7-3
	SUGCT	ENST00000416370.2	TSL:1	c.301C>G	p.Arg101Gly	missense	Exon 4 of 13	ENSP00000393032.2	H0Y4N1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446516 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718670

African (AFR) AF: 0.00 AC: 0 AN: 32536

American (AMR) AF: 0.00 AC: 0 AN: 41976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25776

East Asian (EAS) AF: 0.00 AC: 0 AN: 39054

South Asian (SAS) AF: 0.00 AC: 0 AN: 81556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1106866

Other (OTH) AF: 0.00 AC: 0 AN: 59848

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.6
PROVEAN	Pathogenic	-6.7	D
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.95
gMVP		0.69
Mutation Taster		=29/71	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs137852862;

hg19: chr7-40228168;