rs232775

Variant names:

• chr1-58658874-A-G
• rs232775
• ENST00000493821.6:n.3659T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-58658874-A-G
• chr1-58658874-A-T

Variant summary

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

The ENST00000493821.6(MYSM1):​n.3659T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,366 control chromosomes in the GnomAD database, including 29,907 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 0.63 (29907 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: MYSM1 ENST00000493821.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000493821.6. 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.*1123T>C		3_prime_UTR	Exon 20 of 20	NP_001078956.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYSM1	ENST00000493821.6	TSL:1	n.3659T>C		non_coding_transcript_exon	Exon 16 of 16
	MYSM1	ENST00000472487.6	TSL:1 MANE Select	c.*1123T>C		3_prime_UTR	Exon 20 of 20	ENSP00000418734.1
	MYSM1	ENST00000665648.1		n.*1974T>C		non_coding_transcript_exon	Exon 20 of 20	ENSP00000499586.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94725 AN: 151248 Hom.: 29867 Cov.: 28

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.571

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.626 AC: 94819 AN: 151366 Hom.: 29907 Cov.: 28 AF XY: 0.632 AC XY: 46684 AN XY: 73878

African (AFR) AF: 0.687 AC: 28319 AN: 41222

American (AMR) AF: 0.620 AC: 9420 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1791 AN: 3456

East Asian (EAS) AF: 0.637 AC: 3274 AN: 5142

South Asian (SAS) AF: 0.609 AC: 2925 AN: 4802

European-Finnish (FIN) AF: 0.712 AC: 7442 AN: 10446

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39842 AN: 67822

Other (OTH) AF: 0.572 AC: 1197 AN: 2092

Alfa AF: 0.595 Hom.: 13794

Bravo AF: 0.620

Asia WGS AF: 0.640 AC: 2224 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.69
PhyloP100		-0.63
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: rs232775; hg19: chr1-59124546;