Genetic Variant NM_001193424.2:c.121A>G (chr10-14881589-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.20

Publications

0 publications found

Variant links:

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]

SUV39H2 links:

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ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUV39H2	NM_001193424.2 link	c.121A>G	p.Lys41Glu	missense_variant	Exon 2 of 6	ENST00000354919.11	NP_001180353.1	Q9H5I1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUV39H2	ENST00000354919.11 link	c.121A>G	p.Lys41Glu	missense_variant	Exon 2 of 6	5	NM_001193424.2	ENSP00000346997.6		Q9H5I1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1452134

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33054

American (AMR)

AF:

0.00

AC:

AN:

42828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25954

East Asian (EAS)

AF:

0.0000511

AC:

AN:

39160

South Asian (SAS)

AF:

0.00

AC:

AN:

84168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109084

Other (OTH)

AF:

0.00

AC:

AN:

60006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.121A>G (p.K41E) alteration is located in exon 2 (coding exon 2) of the SUV39H2 gene. This alteration results from a A to G substitution at nucleotide position 121, causing the lysine (K) at amino acid position 41 to be replaced by a glutamic acid (E). 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

0.16

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

0.061

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

D;D

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.35

T;T

MetaSVM

Uncertain

0.73

MutationAssessor

Benign

2.0

M;M

PhyloP100

6.2

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.46

N;N

REVEL

Uncertain

0.51

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.014

D;T

Polyphen

0.21

B;.

Vest4

0.34

MutPred

0.46

Loss of methylation at K41 (P = 0.0061);Loss of methylation at K41 (P = 0.0061);

MVP

0.75

MPC

1.4

ClinPred

0.91

GERP RS

4.9

PromoterAI

0.025

Neutral

(source)

Varity_R

0.25

gMVP

0.57

Mutation Taster

=63/37

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over