17-31937264-C-A

Variant names:

• chr17-31937264-C-A
• rs760726816
• NM_015355.4:c.18C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015355.4(SUZ12):​c.18C>A​(p.His6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000805 in 1,242,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. H6D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: SUZ12 NM_015355.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24876663).

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.18C>A	p.His6Gln	missense	Exon 1 of 16	NP_056170.2	Q15022
	SUZ12	NM_001321207.2		c.18C>A	p.His6Gln	missense	Exon 1 of 15	NP_001308136.1	J3QQW9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUZ12	ENST00000322652.10	TSL:1 MANE Select	c.18C>A	p.His6Gln	missense	Exon 1 of 16	ENSP00000316578.5	Q15022
	SUZ12	ENST00000580398.2	TSL:1	c.18C>A	p.His6Gln	missense	Exon 1 of 15	ENSP00000463936.1	J3QQW9
	SUZ12	ENST00000934319.1		c.18C>A	p.His6Gln	missense	Exon 1 of 17	ENSP00000604378.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 8.05e-7 AC: 1 AN: 1242604 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 607700

African (AFR) AF: 0.00 AC: 0 AN: 23796

American (AMR) AF: 0.00 AC: 0 AN: 9974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19056

East Asian (EAS) AF: 0.0000360 AC: 1 AN: 27772

South Asian (SAS) AF: 0.00 AC: 0 AN: 58152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1017244

Other (OTH) AF: 0.00 AC: 0 AN: 51408

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.83	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.60	N
PhyloP100		2.1
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.15
Sift	Benign	0.089	T
Sift4G	Benign	0.29	T
Polyphen		0.010	B
Vest4		0.39
MutPred		0.15		Gain of glycosylation at P3 (P = 0.1298)
MVP		0.48
MPC		0.92
ClinPred		0.88	D
GERP RS		3.5
PromoterAI		0.010	Neutral
Varity_R		0.25
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

Other links and lift over

dbSNP: rs760726816; hg19: chr17-30264283;