NM_015355.4:c.18C>G

Variant names:

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

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>G​(p.His6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. 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)
• Consequence: SUZ12 NM_015355.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.2526058).

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>G	p.His6Gln	missense	Exon 1 of 16	NP_056170.2	Q15022
	SUZ12	NM_001321207.2		c.18C>G	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>G	p.His6Gln	missense	Exon 1 of 16	ENSP00000316578.5	Q15022
	SUZ12	ENST00000580398.2	TSL:1	c.18C>G	p.His6Gln	missense	Exon 1 of 15	ENSP00000463936.1	J3QQW9
	SUZ12	ENST00000934319.1		c.18C>G	p.His6Gln	missense	Exon 1 of 17	ENSP00000604378.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

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	23
DANN	Benign	0.89
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.75	D
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		0.50
MPC		0.92
ClinPred		0.79	D
GERP RS		3.5
PromoterAI		-0.0092	Neutral
Varity_R		0.25
gMVP		0.12
Mutation Taster		=75/25	polymorphism

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;