rs368779259

Variant names:

• chrX-48700340-C-T
• rs368779259
• NM_003173.4:c.415C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-48700340-C-T
• chrX-48700340-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003173.4(SUV39H1):​c.415C>T​(p.Arg139Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,210,748 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: SUV39H1 NM_003173.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.831
• Publications: 2 publications found

Genes affected

SUV39H1 (HGNC:11479): (SUV39H1 histone lysine methyltransferase) This gene encodes an evolutionarily-conserved protein containing an N-terminal chromodomain and a C-terminal SET domain. The encoded protein is a histone methyltransferase that trimethylates lysine 9 of histone H3, which results in transcriptional gene silencing. Loss of function of this gene disrupts heterochromatin formation and may cause chromosome instability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ENSG00000232828 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24381617).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003173.4. 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
	SUV39H1	NM_003173.4	MANE Select	c.415C>T	p.Arg139Cys	missense	Exon 3 of 6	NP_003164.1	O43463-1
	SUV39H1	NM_001282166.2		c.448C>T	p.Arg150Cys	missense	Exon 3 of 6	NP_001269095.1	O43463-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUV39H1	ENST00000376687.4	TSL:1 MANE Select	c.415C>T	p.Arg139Cys	missense	Exon 3 of 6	ENSP00000365877.4	O43463-1
	SUV39H1	ENST00000337852.10	TSL:2	c.448C>T	p.Arg150Cys	missense	Exon 3 of 6	ENSP00000337976.6	O43463-2
	SUV39H1	ENST00000936593.1		c.409C>T	p.Arg137Cys	missense	Exon 3 of 6	ENSP00000606652.1

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 3 AN: 112629 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000564

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 182303 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098119 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 363481

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54115

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 842079

Other (OTH) AF: 0.00 AC: 0 AN: 46091

GnomAD4 genome AF: 0.0000266 AC: 3 AN: 112629 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34773

African (AFR) AF: 0.00 AC: 0 AN: 30991

American (AMR) AF: 0.00 AC: 0 AN: 10752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2661

East Asian (EAS) AF: 0.00 AC: 0 AN: 3577

South Asian (SAS) AF: 0.00 AC: 0 AN: 2762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000564 AC: 3 AN: 53237

Other (OTH) AF: 0.00 AC: 0 AN: 1527

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.83
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.36
Sift	Benign	0.17	T
Sift4G	Benign	0.11	T
Polyphen		0.012	B
Vest4		0.40
MVP		0.97
MPC		1.6
ClinPred		0.73	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.28
gMVP		0.97
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs368779259; hg19: chrX-48558731;