rs232795

Variant names:

• chr1-58667596-A-G
• rs232795
• NM_001085487.3:c.1842+251T>C

Variant summary

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

The NM_001085487.3(MYSM1):​c.1842+251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,564 control chromosomes in the GnomAD database, including 6,159 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 0.27 (6159 hom., cov: 30)
• Consequence: MYSM1 NM_001085487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYSM1	NM_001085487.3	MANE Select	c.1842+251T>C		intron	N/A	NP_001078956.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYSM1	ENST00000472487.6	TSL:1 MANE Select	c.1842+251T>C		intron	N/A	ENSP00000418734.1
	MYSM1	ENST00000401044.7	TSL:1	n.1687+251T>C		intron	N/A
	MYSM1	ENST00000493821.6	TSL:1	n.1891+251T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40335 AN: 151446 Hom.: 6140 Cov.: 30

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.267 AC: 40402 AN: 151564 Hom.: 6159 Cov.: 30 AF XY: 0.273 AC XY: 20208 AN XY: 73994

African (AFR) AF: 0.409 AC: 16865 AN: 41250

American (AMR) AF: 0.243 AC: 3705 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3466

East Asian (EAS) AF: 0.238 AC: 1222 AN: 5128

South Asian (SAS) AF: 0.281 AC: 1351 AN: 4800

European-Finnish (FIN) AF: 0.356 AC: 3738 AN: 10492

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12294 AN: 67894

Other (OTH) AF: 0.245 AC: 514 AN: 2102

Alfa AF: 0.207 Hom.: 1868

Bravo AF: 0.262

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.29
PhyloP100		0.35
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: rs232795; hg19: chr1-59133268;