rs2811893

Positions:

• chr1-58696476-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MYSM1	NM_001085487.3	c.69-1269A>G		intron_variant		ENST00000472487.6	NP_001078956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYSM1	ENST00000472487.6	c.69-1269A>G		intron_variant		1	NM_001085487.3	ENSP00000418734	P2

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

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.435

Alfa AF: 0.418 Hom.: 20840

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2811893; hg19: chr1-59162148;