17-31937416-C-T

Variant summary

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

The NM_015355.4(SUZ12):​c.170C>T​(p.Ser57Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000324 in 1,542,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SUZ12
NM_015355.4 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.95
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]

Genome browser will be placed here

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=0.2978355).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SUZ12NM_015355.4 linkc.170C>T p.Ser57Phe 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.170C>T p.Ser57Phe missense_variant Exon 1 of 16 1 NM_015355.4 ENSP00000316578.5 Q15022
SUZ12ENST00000580398.1 linkc.170C>T p.Ser57Phe missense_variant Exon 1 of 15 1 ENSP00000463936.1 J3QQW9

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152100
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000144
AC:
2
AN:
1390784
Hom.:
0
Cov.:
31
AF XY:
0.00000146
AC XY:
1
AN XY:
686020
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000186
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152100
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
May 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.170C>T (p.S57F) alteration is located in exon 1 (coding exon 1) of the SUZ12 gene. This alteration results from a C to T substitution at nucleotide position 170, causing the serine (S) at amino acid position 57 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
0.010
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
25
DANN
Benign
0.96
DEOGEN2
Benign
0.15
T;T
Eigen
Benign
0.042
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.79
T;T
M_CAP
Pathogenic
0.87
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-1.3
N;.
REVEL
Uncertain
0.30
Sift
Uncertain
0.024
D;.
Sift4G
Uncertain
0.020
D;D
Polyphen
0.56
P;.
Vest4
0.24
MutPred
0.32
Loss of glycosylation at S57 (P = 0.004);Loss of glycosylation at S57 (P = 0.004);
MVP
0.55
MPC
1.0
ClinPred
0.64
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.3
Varity_R
0.13
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs1159062569; hg19: chr17-30264435; API