rs4379368

Variant names:

• chr7-40426601-C-T
• rs4379368
• NM_001193313.2:c.817-22686C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193313.2(SUGCT):​c.817-22686C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,026 control chromosomes in the GnomAD database, including 1,590 homozygotes. 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: 𝑓 0.13 (1590 hom., cov: 32)
• Consequence: SUGCT NM_001193313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 30 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: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUGCT	NM_001193313.2	c.817-22686C>T		intron_variant	Intron 9 of 13	ENST00000335693.9	NP_001180242.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUGCT	ENST00000335693.9	c.817-22686C>T		intron_variant	Intron 9 of 13	1	NM_001193313.2	ENSP00000338475.5
SUGCT	ENST00000628514.3	c.817-22686C>T		intron_variant	Intron 9 of 14	1		ENSP00000486291.2
SUGCT	ENST00000416370.2	c.817-22686C>T		intron_variant	Intron 9 of 12	1		ENSP00000393032.2
SUGCT	ENST00000401647.7	c.673-22686C>T		intron_variant	Intron 8 of 12	1		ENSP00000385222.3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18997 AN: 151908 Hom.: 1587 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.108

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.125 AC: 19012 AN: 152026 Hom.: 1590 Cov.: 32 AF XY: 0.128 AC XY: 9521 AN XY: 74284

African (AFR) AF: 0.116 AC: 4798 AN: 41472

American (AMR) AF: 0.103 AC: 1567 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2466 AN: 5140

South Asian (SAS) AF: 0.170 AC: 819 AN: 4812

European-Finnish (FIN) AF: 0.155 AC: 1638 AN: 10558

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7048 AN: 67986

Other (OTH) AF: 0.110 AC: 232 AN: 2112

Alfa AF: 0.116 Hom.: 2227

Bravo AF: 0.125

Asia WGS AF: 0.285 AC: 990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.7
DANN	Benign	0.76
PhyloP100		-0.088
Mutation Taster		=100/0	polymorphism (auto)

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: rs4379368; hg19: chr7-40466200;