10-14881511-C-A

Variant names:

• chr10-14881511-C-A
• rs1406036945
• NM_001193424.2:c.43C>A

Variant summary

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

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
• 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.43C>A	p.Pro15Thr	missense	Exon 2 of 6	NP_001180353.1	Q9H5I1-1
	SUV39H2	NM_001193426.2		c.43C>A	p.Pro15Thr	missense	Exon 2 of 6	NP_001180355.1	Q9H5I1-3
	SUV39H2	NM_001193425.2		c.-138C>A		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.43C>A	p.Pro15Thr	missense	Exon 2 of 6	ENSP00000346997.6	Q9H5I1-1
	SUV39H2	ENST00000378325.7	TSL:1	c.43C>A	p.Pro15Thr	missense	Exon 2 of 6	ENSP00000367576.3	Q9H5I1-3
	SUV39H2	ENST00000313519.9	TSL:1	c.-4+2384C>A		intron	N/A	ENSP00000319208.5	Q9H5I1-2

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30956

American (AMR) AF: 0.00 AC: 0 AN: 35388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24484

East Asian (EAS) AF: 0.0000271 AC: 1 AN: 36938

South Asian (SAS) AF: 0.00 AC: 0 AN: 75846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5516

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088930

Other (OTH) AF: 0.00 AC: 0 AN: 57804

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.2
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.0	N
REVEL	Pathogenic	0.74
Sift	Benign	0.17	T
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.61		Loss of loop (P = 0.2237)
MVP		0.87
MPC		2.2
ClinPred		0.80	D
GERP RS		5.9
PromoterAI		-0.0025	Neutral
Varity_R		0.16
gMVP		0.68
Mutation Taster		=34/66	disease causing

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

Other links and lift over

dbSNP: rs1406036945; hg19: chr10-14923510;