chrX-48698973-C-A

Variant names:

• chrX-48698973-C-A
• NM_003173.4:c.91C>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.91C>A​(p.Pro31Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SUV39H1 NM_003173.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.742
• Publications: 0 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=0.21370387).

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.91C>A	p.Pro31Thr	missense	Exon 2 of 6	NP_003164.1	O43463-1
	SUV39H1	NM_001282166.2		c.124C>A	p.Pro42Thr	missense	Exon 2 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.91C>A	p.Pro31Thr	missense	Exon 2 of 6	ENSP00000365877.4	O43463-1
	SUV39H1	ENST00000337852.10	TSL:2	c.124C>A	p.Pro42Thr	missense	Exon 2 of 6	ENSP00000337976.6	O43463-2
	SUV39H1	ENST00000936593.1		c.91C>A	p.Pro31Thr	missense	Exon 2 of 6	ENSP00000606652.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

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	0.092
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.36	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.74
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.24
Sift	Benign	0.30	T
Sift4G	Benign	0.28	T
Polyphen		0.0040	B
Vest4		0.16
MutPred		0.41		Loss of stability (P = 0.0496)
MVP		0.81
MPC		1.4
ClinPred		0.089	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.69
Mutation Taster		=93/7	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

hg19: chrX-48557364;