Genetic Variant MYSM1:p.Glu825Lys (chr1-58660011-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001085487.3(MYSM1):c.2473G>A(p.Glu825Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,575,666 control chromosomes in the GnomAD database, including 35,092 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Synonymous variant affecting the same amino acid position (i.e. E825E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.27 ( 6197 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28895 hom. )

Consequence

MYSM1
NM_001085487.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.137

Variant links:

Genes affected

MYSM1 (HGNC:29401): (Myb like, SWIRM and MPN domains 1) Enables histone binding activity; peptidase activity; and transcription coactivator activity. Involved in several processes, including chromatin remodeling; monoubiquitinated histone H2A deubiquitination; and positive regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. Part of protein-containing complex. Implicated in diabetic retinopathy. [provided by Alliance of Genome Resources, Apr 2022]

MYSM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013670623).

BP6

Variant 1-58660011-C-T is Benign according to our data. Variant chr1-58660011-C-T is described in ClinVar as [Benign]. Clinvar id is 1169778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYSM1	NM_001085487.3 link	c.2473G>A	p.Glu825Lys	missense_variant	Exon 20 of 20	ENST00000472487.6	NP_001078956.1	Q5VVJ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYSM1	ENST00000472487.6 link	c.2473G>A	p.Glu825Lys	missense_variant	Exon 20 of 20	1	NM_001085487.3	ENSP00000418734.1		Q5VVJ2-1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40489

AN:

151764

Hom.:

6178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.357

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.242

GnomAD3 exomes

AF:

0.233

AC:

53391

AN:

228820

Hom.:

6890

AF XY:

0.230

AC XY:

28574

AN XY:

124410

show subpopulations

Gnomad AFR exome

AF:

0.409

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.245

Gnomad SAS exome

AF:

0.264

Gnomad FIN exome

AF:

0.345

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.192

AC:

273326

AN:

1423784

Hom.:

28895

Cov.:

AF XY:

0.194

AC XY:

137183

AN XY:

708410

show subpopulations

Gnomad4 AFR exome

AF:

0.412

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.259

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.267

AC:

40556

AN:

151882

Hom.:

6197

Cov.:

AF XY:

0.274

AC XY:

20309

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.409

Gnomad4 AMR

AF:

0.243

Gnomad4 ASJ

AF:

0.178

Gnomad4 EAS

AF:

0.238

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.357

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.192

Hom.:

7636

Bravo

AF:

0.262

TwinsUK

AF:

0.168

AC:

622

ALSPAC

AF:

0.167

AC:

645

ESP6500AA

AF:

0.389

AC:

1406

ESP6500EA

AF:

0.171

AC:

1396

ExAC

AF:

0.235

AC:

28425

Asia WGS

AF:

0.279

AC:

969

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0032

T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.64

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.5

L;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.072

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.13

T;T

Polyphen

0.0050

B;.

Vest4

0.083

MPC

0.15

ClinPred

0.027

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.18

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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