rs232885

Variant names:

• chr1-58646385-C-A
• rs232885
• ENST00000655340.1:c.*50+42G>T

Variant summary

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

The ENST00000655340.1(MYSM1):​c.*50+42G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,092 control chromosomes in the GnomAD database, including 6,334 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 (6334 hom., cov: 32)
• Consequence: MYSM1 ENST00000655340.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• Publications: 5 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: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, ClinGen, 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000655340.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYSM1	ENST00000655340.1		c.*50+42G>T		intron	N/A	ENSP00000499373.1	A0A590UJD8
	ENSG00000283445	ENST00000637377.2	TSL:5	n.162-68447C>A		intron	N/A
	ENSG00000283445	ENST00000767021.1		n.189-68447C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40801 AN: 151974 Hom.: 6317 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.269 AC: 40867 AN: 152092 Hom.: 6334 Cov.: 32 AF XY: 0.275 AC XY: 20417 AN XY: 74332

African (AFR) AF: 0.415 AC: 17230 AN: 41490

American (AMR) AF: 0.244 AC: 3733 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1230 AN: 5166

South Asian (SAS) AF: 0.282 AC: 1361 AN: 4820

European-Finnish (FIN) AF: 0.357 AC: 3766 AN: 10560

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12318 AN: 67982

Other (OTH) AF: 0.244 AC: 514 AN: 2108

Alfa AF: 0.162 Hom.: 489

Bravo AF: 0.264

Asia WGS AF: 0.278 AC: 967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.80
PhyloP100		0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs232885;

hg19: chr1-59112057;