NM_001193313.2:c.514C>G

Variant names:

• chr7-40237664-C-G
• rs137852861
• NM_001193313.2:c.514C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001193313.2(SUGCT):​c.514C>G​(p.Arg172Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,654 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: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SUGCT NM_001193313.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• 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: PanelApp Australia, Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000300259 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.924

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.514C>G	p.Arg172Gly	missense	Exon 7 of 14	NP_001180242.2	Q9HAC7-1
	SUGCT	NM_001193311.2		c.514C>G	p.Arg172Gly	missense	Exon 7 of 15	NP_001180240.2	Q9HAC7-3
	SUGCT	NM_024728.3		c.403C>G	p.Arg135Gly	missense	Exon 7 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.514C>G	p.Arg172Gly	missense	Exon 7 of 14	ENSP00000338475.5	Q9HAC7-1
	SUGCT	ENST00000628514.3	TSL:1	c.514C>G	p.Arg172Gly	missense	Exon 7 of 15	ENSP00000486291.2	Q9HAC7-3
	SUGCT	ENST00000416370.2	TSL:1	c.514C>G	p.Arg172Gly	missense	Exon 7 of 13	ENSP00000393032.2	H0Y4N1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461654 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727122

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111828

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.30	N
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.20
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.96	D
Vest4		0.87
MutPred		0.78		Gain of catalytic residue at P175 (P = 0.0696)
MVP		0.33
ClinPred		1.0	D
GERP RS		-0.42
Varity_R		0.82
gMVP		0.70
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs137852861; hg19: chr7-40277263;