rs1833040878

Variant names:

• chr10-14881589-A-G
• rs1833040878
• NM_001193424.2:c.121A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001193424.2(SUV39H2):​c.121A>G​(p.Lys41Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,452,134 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SUV39H2 NM_001193424.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.20
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3516357).

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.121A>G	p.Lys41Glu	missense	Exon 2 of 6	NP_001180353.1	Q9H5I1-1
	SUV39H2	NM_001193426.2		c.121A>G	p.Lys41Glu	missense	Exon 2 of 6	NP_001180355.1	Q9H5I1-3
	SUV39H2	NM_001193425.2		c.-60A>G		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.121A>G	p.Lys41Glu	missense	Exon 2 of 6	ENSP00000346997.6	Q9H5I1-1
	SUV39H2	ENST00000378325.7	TSL:1	c.121A>G	p.Lys41Glu	missense	Exon 2 of 6	ENSP00000367576.3	Q9H5I1-3
	SUV39H2	ENST00000313519.9	TSL:1	c.-4+2462A>G		intron	N/A	ENSP00000319208.5	Q9H5I1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452134 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 722266

African (AFR) AF: 0.00 AC: 0 AN: 33054

American (AMR) AF: 0.00 AC: 0 AN: 42828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.0000511 AC: 2 AN: 39160

South Asian (SAS) AF: 0.00 AC: 0 AN: 84168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109084

Other (OTH) AF: 0.00 AC: 0 AN: 60006

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.061
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	0.73	D
MutationAssessor	Benign	2.0	M
PhyloP100		6.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.46	N
REVEL	Uncertain	0.51
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.014	D
Polyphen		0.21	B
Vest4		0.34
MutPred		0.46		Loss of methylation at K41 (P = 0.0061)
MVP		0.75
MPC		1.4
ClinPred		0.91	D
GERP RS		4.9
PromoterAI		0.025	Neutral
Varity_R		0.25
gMVP		0.57
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1833040878; hg19: chr10-14923588;