Genetic Variant SUZ12:p.Ser37Leu (chr17-31937356-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015355.4(SUZ12):c.110C>T(p.Ser37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000801 in 1,497,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000059 ( 0 hom. )

Consequence

SUZ12
NM_015355.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

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]

SUZ12 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26015204).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUZ12	NM_015355.4 link	c.110C>T	p.Ser37Leu	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
SUZ12	ENST00000322652.10 link	c.110C>T	p.Ser37Leu	missense_variant	Exon 1 of 16	1	NM_015355.4	ENSP00000316578.5		Q15022
SUZ12	ENST00000580398.1 link	c.110C>T	p.Ser37Leu	missense_variant	Exon 1 of 15	1		ENSP00000463936.1		J3QQW9

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.00000594

AC:

AN:

1345778

Hom.:

Cov.:

AF XY:

0.00000603

AC XY:

AN XY:

662994

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:

0.00000756

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151870

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.0000484

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

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

May 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.110C>T (p.S37L) 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 110, causing the serine (S) at amino acid position 37 to be replaced by a leucine (L). 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

0.18

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.026

Eigen_PC

Benign

0.092

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.78

T;T

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.2

L;.

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.25

Sift

Uncertain

0.018

D;.

Sift4G

Uncertain

0.021

D;D

Polyphen

0.33

B;.

Vest4

0.16

MutPred

0.15

Loss of glycosylation at S37 (P = 8e-04);Loss of glycosylation at S37 (P = 8e-04);

MVP

0.55

MPC

0.82

ClinPred

0.61

GERP RS

4.7

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.4

Varity_R

0.23

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over