rs752462796

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017841.4(SDHAF2):​c.194C>A​(p.Thr65Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SDHAF2
NM_017841.4 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31616104).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SDHAF2NM_017841.4 linkuse as main transcriptc.194C>A p.Thr65Asn missense_variant 2/4 ENST00000301761.7 NP_060311.1 Q9NX18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SDHAF2ENST00000301761.7 linkuse as main transcriptc.194C>A p.Thr65Asn missense_variant 2/41 NM_017841.4 ENSP00000301761.3 Q9NX18
ENSG00000256591ENST00000541135.5 linkuse as main transcriptc.194C>A p.Thr65Asn missense_variant 2/54 ENSP00000443130.1 F5H5T6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
.;T;.;.;.
Eigen
Benign
0.093
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.93
D;T;D;D;D
M_CAP
Benign
0.077
D
MetaRNN
Benign
0.32
T;T;T;T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.0
.;M;.;.;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-2.3
N;N;.;.;D
REVEL
Uncertain
0.32
Sift
Benign
0.044
D;D;.;.;D
Sift4G
Uncertain
0.060
T;T;D;D;D
Polyphen
0.83
.;P;.;.;.
Vest4
0.29, 0.28, 0.30, 0.30
MutPred
0.23
Loss of phosphorylation at T65 (P = 0.0337);Loss of phosphorylation at T65 (P = 0.0337);Loss of phosphorylation at T65 (P = 0.0337);Loss of phosphorylation at T65 (P = 0.0337);Loss of phosphorylation at T65 (P = 0.0337);
MVP
0.50
MPC
0.20
ClinPred
0.78
D
GERP RS
5.3
Varity_R
0.59
gMVP
0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-61205254; API