Variant 2-84423732-AT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_003849.4(SUCLG1):c.*13del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,542,280 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 21 hom. )

Consequence

SUCLG1
NM_003849.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: -0.846

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 Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000463 (70/151176) while in subpopulation SAS AF= 0.0108 (51/4742). AF 95% confidence interval is 0.0084. There are 0 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCLG1	NM_003849.4 linkuse as main transcript	c.*13del		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.*13del	3_prime_UTR_variant	9/9	1	NM_003849.4	ENSP00000377446	P1
SUCLG1	ENST00000484365.1 linkuse as main transcript	n.1562del	non_coding_transcript_exon_variant	2/2	2
SUCLG1	ENST00000491123.5 linkuse as main transcript	n.900del	non_coding_transcript_exon_variant	4/4	3
SUCLG1	ENST00000651342.1 linkuse as main transcript	c.*494del	3_prime_UTR_variant, NMD_transcript_variant	10/10			ENSP00000498471

Frequencies

GnomAD3 genomes

AF:

0.000443

AC:

AN:

151072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0107

Gnomad FIN

AF:

0.000288

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.000968

GnomAD4 exome

AF:

0.00112

AC:

1554

AN:

1391104

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1009

AN XY:

691482

show subpopulations

Gnomad4 AFR exome

AF:

0.000374

Gnomad4 AMR exome

AF:

0.000926

Gnomad4 ASJ exome

AF:

0.0000406

Gnomad4 EAS exome

AF:

0.000263

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.000295

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000463

AC:

AN:

151176

Hom.:

Cov.:

AF XY:

0.000690

AC XY:

AN XY:

73862

show subpopulations

Gnomad4 AFR

AF:

0.0000970

Gnomad4 AMR

AF:

0.0000660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.000288

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.000959

Bravo

AF:

0.000166

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mitochondrial DNA depletion syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Mitochondrial DNA depletion syndrome 9

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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