17-31937262-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015355.4(SUZ12):​c.16C>G​(p.His6Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H6Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Consequence

SUZ12
NM_015355.4 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38
Variant links:
Genes affected
SUZ12 (HGNC:17101): (SUZ12 polycomb repressive complex 2 subunit) This zinc finger gene has been identified at the breakpoints of a recurrent chromosomal translocation reported in endometrial stromal sarcoma. Recombination of these breakpoints results in the fusion of this gene and JAZF1. The protein encoded by this gene contains a zinc finger domain in the C terminus of the coding region. [provided by RefSeq, Jul 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SUZ12NM_015355.4 linkc.16C>G p.His6Asp missense_variant Exon 1 of 16 ENST00000322652.10 NP_056170.2 Q15022

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SUZ12ENST00000322652.10 linkc.16C>G p.His6Asp missense_variant Exon 1 of 16 1 NM_015355.4 ENSP00000316578.5 Q15022
SUZ12ENST00000580398.1 linkc.16C>G p.His6Asp missense_variant Exon 1 of 15 1 ENSP00000463936.1 J3QQW9

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Jul 15, 2022
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
25
DANN
Benign
0.93
DEOGEN2
Benign
0.11
T;T
Eigen
Benign
-0.018
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.63
T;T
M_CAP
Pathogenic
0.87
D
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
1.1
L;.
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-1.8
N;.
REVEL
Uncertain
0.38
Sift
Benign
0.049
D;.
Sift4G
Uncertain
0.012
D;D
Polyphen
0.23
B;.
Vest4
0.53
MutPred
0.18
Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP
0.80
MPC
1.2
ClinPred
0.90
D
GERP RS
4.5
Varity_R
0.38
gMVP
0.26

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: chr17-30264281; API