X-48700340-C-A

Variant names:

• chrX-48700340-C-A
• rs368779259
• NM_003173.4:c.415C>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>A​(p.Arg139Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. R139C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: SUV39H1 NM_003173.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.18731055).

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>A	p.Arg139Ser	missense	Exon 3 of 6	NP_003164.1	O43463-1
	SUV39H1	NM_001282166.2		c.448C>A	p.Arg150Ser	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>A	p.Arg139Ser	missense	Exon 3 of 6	ENSP00000365877.4	O43463-1
	SUV39H1	ENST00000337852.10	TSL:2	c.448C>A	p.Arg150Ser	missense	Exon 3 of 6	ENSP00000337976.6	O43463-2
	SUV39H1	ENST00000936593.1		c.409C>A	p.Arg137Ser	missense	Exon 3 of 6	ENSP00000606652.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.83
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.36	N
REVEL	Uncertain	0.36
Sift	Benign	0.65	T
Sift4G	Benign	0.81	T
Polyphen		0.023	B
Vest4		0.36
MutPred		0.46		Loss of catalytic residue at R139 (P = 0.0062)
MVP		0.97
MPC		1.6
ClinPred		0.65	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.44
gMVP		0.98
Mutation Taster		=64/36	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;