X-48695823-G-A

Position:

• chrX-48695823-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001282166.2(SUV39H1):​c.4G>A​(p.Val2Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000883 in 1,042,081 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 50 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000088 (0 hom. 50 hem.)
• Consequence: SUV39H1 NM_001282166.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.390

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026428193).
• BP6: Variant X-48695823-G-A is Benign according to our data. Variant chrX-48695823-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 50 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUV39H1	NM_001282166.2	c.4G>A	p.Val2Met	missense_variant	1/6		NP_001269095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUV39H1	ENST00000337852.10	c.4G>A	p.Val2Met	missense_variant	1/6	2		ENSP00000337976.6

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.000235 AC: 22 AN: 93446 Hom.: 0 AF XY: 0.000455 AC XY: 16 AN XY: 35156

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 SAS exome AF: 0.00158

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000883 AC: 92 AN: 1042081 Hom.: 0 Cov.: 31 AF XY: 0.000147 AC XY: 50 AN XY: 341261

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00182

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000226

GnomAD4 genome Cov.: 24

Alfa AF: 0.000223 Hom.: 0

ExAC AF: 0.000574 AC: 10

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SUV39H1: PP2, PP3, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.8
DANN	Benign	0.96
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.026	T
MetaSVM	Uncertain	-0.17	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Vest4		0.041
MutPred		0.18		Gain of solvent accessibility (P = 0.0713);
MVP		0.30
ClinPred		0.018	T
GERP RS		1.4
gMVP		0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs782793692; hg19: chrX-48554214;