11-61430097-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000541135(ENSG00000256591):​c.-50G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,612,402 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 6 hom. )

Consequence

ENSG00000256591
ENST00000541135 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.97
Variant links:
Genes affected
SDHAF2 (HGNC:26034): (succinate dehydrogenase complex assembly factor 2) This gene encodes a mitochondrial assembly factor needed for the flavination of a succinate dehydrogenase complex subunit (SDHA), which is required for activity of the succinate dehydrogenase complex. Mutations in this gene are associated with paraganglioma. [provided by RefSeq, May 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 11-61430097-G-T is Benign according to our data. Variant chr11-61430097-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 513739.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SDHAF2NM_017841.4 linkc.-50G>T upstream_gene_variant ENST00000301761.7 NP_060311.1 Q9NX18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENSG00000256591ENST00000541135 linkc.-50G>T 5_prime_UTR_premature_start_codon_gain_variant 1/54 ENSP00000443130.1 F5H5T6
ENSG00000256591ENST00000541135 linkc.-50G>T 5_prime_UTR_variant 1/54 ENSP00000443130.1 F5H5T6
SDHAF2ENST00000301761.7 linkc.-50G>T upstream_gene_variant 1 NM_017841.4 ENSP00000301761.3 Q9NX18

Frequencies

GnomAD3 genomes
AF:
0.00138
AC:
210
AN:
152276
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000357
AC:
88
AN:
246400
Hom.:
0
AF XY:
0.000322
AC XY:
43
AN XY:
133610
show subpopulations
Gnomad AFR exome
AF:
0.00519
Gnomad AMR exome
AF:
0.0000877
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000902
Gnomad OTH exome
AF:
0.000506
GnomAD4 exome
AF:
0.000155
AC:
226
AN:
1460012
Hom.:
6
Cov.:
30
AF XY:
0.000151
AC XY:
110
AN XY:
726296
show subpopulations
Gnomad4 AFR exome
AF:
0.00595
Gnomad4 AMR exome
AF:
0.000180
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.000282
GnomAD4 genome
AF:
0.00138
AC:
210
AN:
152390
Hom.:
1
Cov.:
33
AF XY:
0.00133
AC XY:
99
AN XY:
74526
show subpopulations
Gnomad4 AFR
AF:
0.00481
Gnomad4 AMR
AF:
0.000457
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000513
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxNov 24, 2017This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
9.7
DANN
Benign
0.83
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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.

Other links and lift over

dbSNP: rs200379024; hg19: chr11-61197569; API