17-31937332-C-T

Variant names:

• chr17-31937332-C-T
• NM_015355.4:c.86C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015355.4(SUZ12):​c.86C>T​(p.Ala29Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,315,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A29P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SUZ12 NM_015355.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27070296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUZ12	NM_015355.4	c.86C>T	p.Ala29Val	missense_variant	Exon 1 of 16	ENST00000322652.10	NP_056170.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUZ12	ENST00000322652.10	c.86C>T	p.Ala29Val	missense_variant	Exon 1 of 16	1	NM_015355.4	ENSP00000316578.5
SUZ12	ENST00000580398.1	c.86C>T	p.Ala29Val	missense_variant	Exon 1 of 15	1		ENSP00000463936.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1315756 Hom.: 0 Cov.: 31 AF XY: 0.00000309 AC XY: 2 AN XY: 646806

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: 0.0000285

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.86C>T (p.A29V) 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 86, causing the alanine (A) at amino acid position 29 to be replaced by a valine (V). 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	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.094	T;T
Eigen	Benign	0.066
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.73	T;T
M_CAP	Pathogenic	0.78	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.72	N;.
REVEL	Benign	0.22
Sift	Benign	0.54	T;.
Sift4G	Uncertain	0.024	D;D
Polyphen		0.81	P;.
Vest4		0.31
MutPred		0.29		Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);
MVP		0.53
MPC		0.92
ClinPred		0.84	D
GERP RS		4.9
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.0
Varity_R		0.19
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-30264351;