10-14881529-G-T

Variant names:

• chr10-14881529-G-T
• rs781513024
• NM_001193424.2:c.61G>T

Variant summary

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

The NM_001193424.2(SUV39H2):​c.61G>T​(p.Asp21Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,439,666 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D21H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SUV39H2 NM_001193424.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.64
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193424.2. 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
	SUV39H2	NM_001193424.2	MANE Select	c.61G>T	p.Asp21Tyr	missense	Exon 2 of 6	NP_001180353.1	Q9H5I1-1
	SUV39H2	NM_001193426.2		c.61G>T	p.Asp21Tyr	missense	Exon 2 of 6	NP_001180355.1	Q9H5I1-3
	SUV39H2	NM_001193425.2		c.-120G>T		5_prime_UTR	Exon 2 of 6	NP_001180354.1	Q9H5I1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUV39H2	ENST00000354919.11	TSL:5 MANE Select	c.61G>T	p.Asp21Tyr	missense	Exon 2 of 6	ENSP00000346997.6	Q9H5I1-1
	SUV39H2	ENST00000378325.7	TSL:1	c.61G>T	p.Asp21Tyr	missense	Exon 2 of 6	ENSP00000367576.3	Q9H5I1-3
	SUV39H2	ENST00000313519.9	TSL:1	c.-4+2402G>T		intron	N/A	ENSP00000319208.5	Q9H5I1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439666 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 715778

African (AFR) AF: 0.00 AC: 0 AN: 32426

American (AMR) AF: 0.00 AC: 0 AN: 40606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25584

East Asian (EAS) AF: 0.00 AC: 0 AN: 38530

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103908

Other (OTH) AF: 0.00 AC: 0 AN: 59424

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	32
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	1.8	L
PhyloP100		6.6
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.0	N
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.49
MutPred		0.43		Gain of helix (P = 0.132)
MVP		0.79
MPC		1.9
ClinPred		0.79	D
GERP RS		5.9
PromoterAI		0.060	Neutral
Varity_R		0.26
gMVP		0.71
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs781513024; hg19: chr10-14923528;