Variant X-48700221-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003173.4(SUV39H1):c.296G>A(p.Arg99Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000191 in 1,203,515 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes 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: 0.000018 ( 0 hom. 9 hem. )

Consequence

SUV39H1
NM_003173.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.54

Variant links:

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]

SUV39H1 links:

ENSG00000232828 (HGNC:):

ENSG00000232828 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10486305).

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUV39H1	NM_003173.4 linkuse as main transcript	c.296G>A	p.Arg99Gln	missense_variant	3/6	ENST00000376687.4	NP_003164.1	O43463-1
SUV39H1	NM_001282166.2 linkuse as main transcript	c.329G>A	p.Arg110Gln	missense_variant	3/6		NP_001269095.1	O43463-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SUV39H1	ENST00000376687.4 linkuse as main transcript	c.296G>A	p.Arg99Gln	missense_variant	3/6	1	NM_003173.4	ENSP00000365877.4	O43463-1
SUV39H1	ENST00000337852.10 linkuse as main transcript	c.329G>A	p.Arg110Gln	missense_variant	3/6	2		ENSP00000337976.6	O43463-2
ENSG00000232828	ENST00000416061.1 linkuse as main transcript	n.610C>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111495

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33705

show subpopulations

Gnomad AFR

AF:

0.0000654

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000182

AC:

AN:

164970

Hom.:

AF XY:

0.00

AC XY:

AN XY:

53368

show subpopulations

Gnomad AFR exome

AF:

0.0000852

Gnomad AMR exome

AF:

0.0000381

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000183

AC:

AN:

1091968

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

358484

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.0000289

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000334

Gnomad4 SAS exome

AF:

0.0000377

Gnomad4 FIN exome

AF:

0.0000250

Gnomad4 NFE exome

AF:

0.0000155

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111547

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33767

show subpopulations

Gnomad4 AFR

AF:

0.0000653

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.296G>A (p.R99Q) alteration is located in exon 3 (coding exon 3) of the SUV39H1 gene. This alteration results from a G to A substitution at nucleotide position 296, causing the arginine (R) at amino acid position 99 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

.;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.10

T;T

MetaSVM

Uncertain

0.062

MutationAssessor

Benign

1.9

.;L

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.35

N;N

REVEL

Benign

0.26

Sift

Benign

0.36

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.22

.;B

Vest4

0.20

MutPred

0.33

.;Loss of catalytic residue at R99 (P = 0.02);

MVP

0.97

MPC

1.4

ClinPred

0.074

GERP RS

4.8

Varity_R

0.40

gMVP

0.81

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over