3-67375866-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003848.4(SUCLG2):​c.1184-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,611,836 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0089 ( 10 hom., cov: 33)
Exomes 𝑓: 0.010 ( 139 hom. )

Consequence

SUCLG2
NM_003848.4 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00007529
2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.01
Variant links:
Genes affected
SUCLG2 (HGNC:11450): (succinate-CoA ligase GDP-forming subunit beta) This gene encodes a GTP-specific beta subunit of succinyl-CoA synthetase. Succinyl-CoA synthetase catalyzes the reversible reaction involving the formation of succinyl-CoA and succinate. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 5 and 12. [provided by RefSeq, Apr 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 3-67375866-G-A is Benign according to our data. Variant chr3-67375866-G-A is described in ClinVar as [Benign]. Clinvar id is 3056433.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00889 (1354/152308) while in subpopulation SAS AF= 0.0251 (121/4826). AF 95% confidence interval is 0.0214. There are 10 homozygotes in gnomad4. There are 668 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SUCLG2NM_003848.4 linkuse as main transcriptc.1184-7C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000307227.10 NP_003839.2
SUCLG2XM_017007420.3 linkuse as main transcriptc.*596C>T 3_prime_UTR_variant 11/11 XP_016862909.1
SUCLG2NM_001177599.2 linkuse as main transcriptc.1184-15098C>T intron_variant NP_001171070.1
SUCLG2XM_047449140.1 linkuse as main transcriptc.1040-7C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant XP_047305096.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SUCLG2ENST00000307227.10 linkuse as main transcriptc.1184-7C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_003848.4 ENSP00000307432 P1Q96I99-1
SUCLG2ENST00000460567.5 linkuse as main transcriptc.456-7C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 ENSP00000417260
SUCLG2ENST00000493112.5 linkuse as main transcriptc.1184-15098C>T intron_variant 1 ENSP00000419325 Q96I99-2

Frequencies

GnomAD3 genomes
AF:
0.00888
AC:
1352
AN:
152190
Hom.:
10
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00275
Gnomad ASJ
AF:
0.0130
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0246
Gnomad FIN
AF:
0.0197
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.0125
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.0104
AC:
2550
AN:
245600
Hom.:
24
AF XY:
0.0116
AC XY:
1545
AN XY:
133060
show subpopulations
Gnomad AFR exome
AF:
0.00157
Gnomad AMR exome
AF:
0.00214
Gnomad ASJ exome
AF:
0.0109
Gnomad EAS exome
AF:
0.000112
Gnomad SAS exome
AF:
0.0220
Gnomad FIN exome
AF:
0.0173
Gnomad NFE exome
AF:
0.0113
Gnomad OTH exome
AF:
0.0104
GnomAD4 exome
AF:
0.0105
AC:
15304
AN:
1459528
Hom.:
139
Cov.:
36
AF XY:
0.0110
AC XY:
7951
AN XY:
725754
show subpopulations
Gnomad4 AFR exome
AF:
0.00170
Gnomad4 AMR exome
AF:
0.00232
Gnomad4 ASJ exome
AF:
0.0119
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0221
Gnomad4 FIN exome
AF:
0.0219
Gnomad4 NFE exome
AF:
0.00985
Gnomad4 OTH exome
AF:
0.0119
GnomAD4 genome
AF:
0.00889
AC:
1354
AN:
152308
Hom.:
10
Cov.:
33
AF XY:
0.00897
AC XY:
668
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00144
Gnomad4 AMR
AF:
0.00274
Gnomad4 ASJ
AF:
0.0130
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0251
Gnomad4 FIN
AF:
0.0197
Gnomad4 NFE
AF:
0.0125
Gnomad4 OTH
AF:
0.00804
Alfa
AF:
0.0110
Hom.:
8
Bravo
AF:
0.00637
Asia WGS
AF:
0.00751
AC:
26
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SUCLG2-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesSep 12, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
3.1
DANN
Benign
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000075
dbscSNV1_RF
Benign
0.0
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.

Other links and lift over

dbSNP: rs185820586; hg19: chr3-67426290; API