7-40237664-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001193313.2(SUGCT):​c.514C>A​(p.Arg172Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SUGCT NM_001193313.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 8 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.102).
• BP7: Synonymous conserved (PhyloP=0.199 with no splicing effect.

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>A	p.Arg172Arg	synonymous	Exon 7 of 14	NP_001180242.2	Q9HAC7-1
	SUGCT	NM_001193311.2		c.514C>A	p.Arg172Arg	synonymous	Exon 7 of 15	NP_001180240.2	Q9HAC7-3
	SUGCT	NM_024728.3		c.403C>A	p.Arg135Arg	synonymous	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>A	p.Arg172Arg	synonymous	Exon 7 of 14	ENSP00000338475.5	Q9HAC7-1
	SUGCT	ENST00000628514.3	TSL:1	c.514C>A	p.Arg172Arg	synonymous	Exon 7 of 15	ENSP00000486291.2	Q9HAC7-3
	SUGCT	ENST00000416370.2	TSL:1	c.514C>A	p.Arg172Arg	synonymous	Exon 7 of 13	ENSP00000393032.2	H0Y4N1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.7
DANN	Benign	0.56
PhyloP100		0.20

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

Other links and lift over

dbSNP: rs137852861; hg19: chr7-40277263; COSMIC: COSV59318017;