rs2811893

Variant names:

• chr1-58696476-T-C
• rs2811893
• NM_001085487.3:c.69-1269A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001085487.3(MYSM1):​c.69-1269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,988 control chromosomes in the GnomAD database, including 11,566 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (11566 hom., cov: 31)
• Consequence: MYSM1 NM_001085487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37
• Publications: 25 publications found

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: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ENSG00000283445 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYSM1	NM_001085487.3	c.69-1269A>G		intron_variant	Intron 1 of 19	ENST00000472487.6	NP_001078956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYSM1	ENST00000472487.6	c.69-1269A>G		intron_variant	Intron 1 of 19	1	NM_001085487.3	ENSP00000418734.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58909 AN: 151870 Hom.: 11557 Cov.: 31

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.437

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.388 AC: 58945 AN: 151988 Hom.: 11566 Cov.: 31 AF XY: 0.382 AC XY: 28341 AN XY: 74268

African (AFR) AF: 0.364 AC: 15097 AN: 41454

American (AMR) AF: 0.384 AC: 5869 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1668 AN: 3466

East Asian (EAS) AF: 0.360 AC: 1860 AN: 5168

South Asian (SAS) AF: 0.391 AC: 1886 AN: 4828

European-Finnish (FIN) AF: 0.285 AC: 3006 AN: 10542

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28050 AN: 67936

Other (OTH) AF: 0.435 AC: 916 AN: 2106

Alfa AF: 0.413 Hom.: 45229

Bravo AF: 0.397

Asia WGS AF: 0.361 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.020
DANN	Benign	0.30
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs2811893; hg19: chr1-59162148;