10-14881511-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001193424.2(SUV39H2):c.43C>A(p.Pro15Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000711 in 1,407,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SUV39H2 NM_001193424.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.23

Genes affected

SUV39H2 (HGNC:17287): (SUV39H2 histone lysine methyltransferase) Enables S-adenosyl-L-methionine binding activity; histone methyltransferase activity (H3-K9 specific); and zinc ion binding activity. Involved in chromatin assembly or disassembly and chromatin remodeling. Acts upstream of or within cellular response to hypoxia and negative regulation of transcription by RNA polymerase II. Located in chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, SUV39H2

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUV39H2	NM_001193424.2	c.43C>A	p.Pro15Thr	missense_variant	2/6	ENST00000354919.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUV39H2	ENST00000354919.11	c.43C>A	p.Pro15Thr	missense_variant	2/6	5	NM_001193424.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1407052 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 699062

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000271

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.43C>A (p.P15T) alteration is located in exon 2 (coding exon 2) of the SUV39H2 gene. This alteration results from a C to A substitution at nucleotide position 43, causing the proline (P) at amino acid position 15 to be replaced by a threonine (T). 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	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.40
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.0	N;N
REVEL	Pathogenic	0.74
Sift	Benign	0.17	T;T
Sift4G	Benign	0.19	T;T
Polyphen		1.0	D;.
Vest4		0.59
MutPred		0.61		Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);
MVP		0.87
MPC		2.2
ClinPred		0.80	D
GERP RS		5.9
Varity_R		0.16
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs1406036945; hg19: chr10-14923510;