9-133357733-A-G
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_017503.5(SURF2):āc.256A>Gā(p.Thr86Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000041 ( 0 hom. )
Consequence
SURF2
NM_017503.5 missense
NM_017503.5 missense
Scores
9
5
2
Clinical Significance
Conservation
PhyloP100: 7.19
Genes affected
SURF2 (HGNC:11475): (surfeit 2) This gene shares a bidirectional promoter with surfeit 1 (SURF1; GeneID: 6834), which is located on the opposite strand. It encodes a conserved protein that is expressed in a variety of tissues. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.981
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SURF2 | NM_017503.5 | c.256A>G | p.Thr86Ala | missense_variant | 3/6 | ENST00000371964.5 | NP_059973.4 | |
SURF2 | NM_001278928.2 | c.256A>G | p.Thr86Ala | missense_variant | 3/6 | NP_001265857.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SURF2 | ENST00000371964.5 | c.256A>G | p.Thr86Ala | missense_variant | 3/6 | 1 | NM_017503.5 | ENSP00000361032.4 | ||
SURF2 | ENST00000486887.1 | n.158A>G | non_coding_transcript_exon_variant | 2/3 | 3 | |||||
SURF2 | ENST00000495524.5 | n.437A>G | non_coding_transcript_exon_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461438Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727002
GnomAD4 exome
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6
AN:
1461438
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31
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2
AN XY:
727002
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2024 | The c.256A>G (p.T86A) alteration is located in exon 3 (coding exon 3) of the SURF2 gene. This alteration results from a A to G substitution at nucleotide position 256, causing the threonine (T) at amino acid position 86 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MutPred
Gain of helix (P = 0.0854);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at