Genetic Variant SUZ12:p.Ala66Thr (chr17-31937442-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015355.4(SUZ12):c.196G>A(p.Ala66Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000551 in 1,541,936 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00056 ( 1 hom. )

Consequence

SUZ12
NM_015355.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008852154).

BP6

Variant 17-31937442-G-A is Benign according to our data. Variant chr17-31937442-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3250500.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000486 (74/152228) while in subpopulation NFE AF= 0.000838 (57/68014). AF 95% confidence interval is 0.000664. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 74 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUZ12	NM_015355.4 link	c.196G>A	p.Ala66Thr	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.196G>A	p.Ala66Thr	missense_variant	Exon 1 of 16	1	NM_015355.4	ENSP00000316578.5		Q15022
SUZ12	ENST00000580398.1 link	c.196G>A	p.Ala66Thr	missense_variant	Exon 1 of 15	1		ENSP00000463936.1		J3QQW9

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000538

AC:

AN:

145000

Hom.:

AF XY:

0.000616

AC XY:

AN XY:

77956

show subpopulations

Gnomad AFR exome

AF:

0.000298

Gnomad AMR exome

AF:

0.000836

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000731

Gnomad NFE exome

AF:

0.000950

Gnomad OTH exome

AF:

0.000482

GnomAD4 exome

AF:

0.000558

AC:

776

AN:

1389708

Hom.:

Cov.:

AF XY:

0.000570

AC XY:

391

AN XY:

685526

show subpopulations

Gnomad4 AFR exome

AF:

0.0000646

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.0000571

Gnomad4 SAS exome

AF:

0.0000760

Gnomad4 FIN exome

AF:

0.000177

Gnomad4 NFE exome

AF:

0.000646

Gnomad4 OTH exome

AF:

0.000642

GnomAD4 genome

AF:

0.000486

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000693

Hom.:

Bravo

AF:

0.000457

ExAC

AF:

0.0000527

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SUZ12: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.039

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.76

T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.0089

T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.3

L;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.68

N;.

REVEL

Benign

0.18

Sift

Benign

0.18

T;.

Sift4G

Uncertain

0.013

D;D

Polyphen

0.099

B;.

Vest4

0.073

MVP

0.35

MPC

0.89

ClinPred

0.014

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.090

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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