Genetic Variant MYSM1:p.Glu779Glu (chr1-58660147-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001085487.3(MYSM1):c.2337G>A(p.Glu779Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

MYSM1
NM_001085487.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.505

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

bone marrow failure syndrome 4
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen

MYSM1 links:

ENSG00000283445 (HGNC:):

ENSG00000283445 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 1-58660147-C-T is Benign according to our data. Variant chr1-58660147-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3680264.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.505 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085487.3. 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
	MYSM1	NM_001085487.3	MANE Select	c.2337G>A	p.Glu779Glu	synonymous	Exon 20 of 20	NP_001078956.1	Q5VVJ2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYSM1	ENST00000472487.6	TSL:1 MANE Select	c.2337G>A	p.Glu779Glu	synonymous	Exon 20 of 20	ENSP00000418734.1	Q5VVJ2-1
MYSM1	ENST00000401044.7	TSL:1	n.2182G>A		non_coding_transcript_exon	Exon 17 of 17
MYSM1	ENST00000493821.6	TSL:1	n.2386G>A		non_coding_transcript_exon	Exon 16 of 16

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000476

AC:

AN:

209982

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000439

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.12e-7

AC:

AN:

1404872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30440

American (AMR)

AF:

0.0000307

AC:

AN:

32594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23514

East Asian (EAS)

AF:

0.00

AC:

AN:

38762

South Asian (SAS)

AF:

0.00

AC:

AN:

77306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5476

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087442

Other (OTH)

AF:

0.00

AC:

AN:

57718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.7

(source)

DANN

Benign

0.55

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over