7-40188429-A-T

Position:

• chr7-40188429-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001193313.2(SUGCT):​c.227-66A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 965,496 control chromosomes in the GnomAD database, including 7,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (738 hom., cov: 23)
  • Exomes 𝑓: 0.11 (6593 hom.)
• Consequence: SUGCT NM_001193313.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0550

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 7-40188429-A-T is Benign according to our data. Variant chr7-40188429-A-T is described in ClinVar as [Benign]. Clinvar id is 1278902.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUGCT	NM_001193313.2	c.227-66A>T		intron_variant		ENST00000335693.9	NP_001180242.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUGCT	ENST00000335693.9	c.227-66A>T		intron_variant		1	NM_001193313.2	ENSP00000338475	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 12371 AN: 120794 Hom.: 739 Cov.: 23

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.0448

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0620

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.108 AC: 91293 AN: 844672 Hom.: 6593 AF XY: 0.106 AC XY: 46121 AN XY: 433682

Gnomad4 AFR exome AF: 0.0209

Gnomad4 AMR exome AF: 0.0540

Gnomad4 ASJ exome AF: 0.0601

Gnomad4 EAS exome AF: 0.0147

Gnomad4 SAS exome AF: 0.0396

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.0932

GnomAD4 genome AF: 0.102 AC: 12364 AN: 120824 Hom.: 738 Cov.: 23 AF XY: 0.100 AC XY: 5772 AN XY: 57654

Gnomad4 AFR AF: 0.0341

Gnomad4 AMR AF: 0.0889

Gnomad4 ASJ AF: 0.0629

Gnomad4 EAS AF: 0.0114

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0345 Hom.: 40

Bravo AF: 0.0817

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs644966; hg19: chr7-40228028; COSMIC: COSV59362263;