17-31937344-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_015355.4(SUZ12):c.98C>T(p.Ala33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000338 in 1,480,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

SUZ12
NM_015355.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.44

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Imagawa-Matsumoto syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics, PanelApp Australia
Weaver syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SUZ12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1915695).

BP6

Variant 17-31937344-C-T is Benign according to our data. Variant chr17-31937344-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3067301.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000217 (33/151896) while in subpopulation NFE AF = 0.000397 (27/67960). AF 95% confidence interval is 0.00028. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 33 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015355.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUZ12	NM_015355.4	MANE Select	c.98C>T	p.Ala33Val	missense	Exon 1 of 16	NP_056170.2	Q15022
	SUZ12	NM_001321207.2		c.98C>T	p.Ala33Val	missense	Exon 1 of 15	NP_001308136.1	J3QQW9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUZ12	ENST00000322652.10	TSL:1 MANE Select	c.98C>T	p.Ala33Val	missense	Exon 1 of 16	ENSP00000316578.5	Q15022
SUZ12	ENST00000580398.2	TSL:1	c.98C>T	p.Ala33Val	missense	Exon 1 of 15	ENSP00000463936.1	J3QQW9
SUZ12	ENST00000934319.1		c.98C>T	p.Ala33Val	missense	Exon 1 of 17	ENSP00000604378.1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.000397

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000231

AC:

AN:

82082

AF XY:

0.000256

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000334

Gnomad OTH exome

AF:

0.000439

GnomAD4 exome

AF:

0.000351

AC:

467

AN:

1328934

Hom.:

Cov.:

AF XY:

0.000332

AC XY:

217

AN XY:

654258

show subpopulations

African (AFR)

AF:

0.0000756

AC:

AN:

26470

American (AMR)

AF:

0.000238

AC:

AN:

25242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22606

East Asian (EAS)

AF:

0.00

AC:

AN:

29384

South Asian (SAS)

AF:

0.00

AC:

AN:

72906

European-Finnish (FIN)

AF:

0.000122

AC:

AN:

40994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3894

European-Non Finnish (NFE)

AF:

0.000420

AC:

442

AN:

1052426

Other (OTH)

AF:

0.000218

AC:

AN:

55012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000217

AC:

AN:

151896

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41374

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

67960

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.000230

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.095

Eigen

Benign

-0.10

Eigen_PC

Benign

0.0023

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.69

PhyloP100

1.4

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.72

REVEL

Uncertain

0.31

Sift

Benign

0.047

Sift4G

Uncertain

0.0080

Polyphen

0.33

Vest4

0.16

MVP

0.45

MPC

0.92

ClinPred

0.18

GERP RS

3.7

PromoterAI

-0.067

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.4

Varity_R

0.14

gMVP

0.22

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over