rs1644370284

Variant names:

• chr1-58660161-TGAAAA-T
• rs1644370284
• NM_001085487.3:c.2329-11_2329-7delTTTTC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001085487.3(MYSM1):​c.2329-11_2329-7delTTTTC variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000803 in 1,370,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: MYSM1 NM_001085487.3 splice_region, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51
• Publications: 0 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen

ENSG00000283445 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2329-11_2329-7delTTTTC		splice_region intron	N/A	NP_001078956.1	Q5VVJ2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYSM1	ENST00000472487.6	TSL:1 MANE Select	c.2329-11_2329-7delTTTTC		splice_region intron	N/A	ENSP00000418734.1	Q5VVJ2-1
	MYSM1	ENST00000401044.7	TSL:1	n.2174-11_2174-7delTTTTC		splice_region intron	N/A
	MYSM1	ENST00000493821.6	TSL:1	n.2378-11_2378-7delTTTTC		splice_region intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000803 AC: 11 AN: 1370456 Hom.: 0 AF XY: 0.00000442 AC XY: 3 AN XY: 678032

African (AFR) AF: 0.00 AC: 0 AN: 29510

American (AMR) AF: 0.00 AC: 0 AN: 29816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22410

East Asian (EAS) AF: 0.00 AC: 0 AN: 37792

South Asian (SAS) AF: 0.00 AC: 0 AN: 71822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5346

European-Non Finnish (NFE) AF: 0.0000103 AC: 11 AN: 1067664

Other (OTH) AF: 0.00 AC: 0 AN: 56022

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

Splicing

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

Other links and lift over

dbSNP: rs1644370284; hg19: chr1-59125833;