Variant chr2-84423583-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003849.4(SUCLG1):c.*163T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 710,918 control chromosomes in the GnomAD database, including 290,493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 52676 hom., cov: 33)

Exomes 𝑓: 0.92 ( 237817 hom. )

Consequence

SUCLG1
NM_003849.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.443

Variant links:

Genes affected

SUCLG1 (HGNC:11449): (succinate-CoA ligase GDP/ADP-forming subunit alpha) This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile lactic acidosis and mitochondrial DNA depletion. [provided by RefSeq, Feb 2010]

SUCLG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-84423583-A-G is Benign according to our data. Variant chr2-84423583-A-G is described in ClinVar as [Benign]. Clinvar id is 337149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCLG1	NM_003849.4 linkuse as main transcript	c.*163T>C		3_prime_UTR_variant	9/9	ENST00000393868.7	NP_003840.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
SUCLG1	ENST00000393868.7 linkuse as main transcript	c.*163T>C	3_prime_UTR_variant	9/9	1	NM_003849.4	ENSP00000377446	P1
SUCLG1	ENST00000484365.1 linkuse as main transcript	n.1712T>C	non_coding_transcript_exon_variant	2/2	2
SUCLG1	ENST00000491123.5 linkuse as main transcript	n.1050T>C	non_coding_transcript_exon_variant	4/4	3
SUCLG1	ENST00000651342.1 linkuse as main transcript	c.*644T>C	3_prime_UTR_variant, NMD_transcript_variant	10/10			ENSP00000498471

Frequencies

GnomAD3 genomes

AF:

0.810

AC:

123161

AN:

152112

Hom.:

52670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.902

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.936

Gnomad EAS

AF:

0.920

Gnomad SAS

AF:

0.909

Gnomad FIN

AF:

0.955

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.933

Gnomad OTH

AF:

0.841

GnomAD4 exome

AF:

0.920

AC:

513825

AN:

558688

Hom.:

237817

Cov.:

AF XY:

0.921

AC XY:

275883

AN XY:

299434

show subpopulations

Gnomad4 AFR exome

AF:

0.504

Gnomad4 AMR exome

AF:

0.930

Gnomad4 ASJ exome

AF:

0.934

Gnomad4 EAS exome

AF:

0.937

Gnomad4 SAS exome

AF:

0.916

Gnomad4 FIN exome

AF:

0.957

Gnomad4 NFE exome

AF:

0.934

Gnomad4 OTH exome

AF:

0.891

GnomAD4 genome

AF:

0.809

AC:

123200

AN:

152230

Hom.:

52676

Cov.:

AF XY:

0.814

AC XY:

60581

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.501

Gnomad4 AMR

AF:

0.888

Gnomad4 ASJ

AF:

0.936

Gnomad4 EAS

AF:

0.920

Gnomad4 SAS

AF:

0.909

Gnomad4 FIN

AF:

0.955

Gnomad4 NFE

AF:

0.933

Gnomad4 OTH

AF:

0.840

Alfa

AF:

0.835

Hom.:

10612

Bravo

AF:

0.793

Asia WGS

AF:

0.887

AC:

3087

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Mitochondrial DNA depletion syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Mitochondrial DNA depletion syndrome 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.1

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over