12-53305201-A-G

Variant names:

• chr12-53305201-A-G
• rs4325348
• NM_021640.4:c.490-707A>G

Variant summary

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

The NM_021640.4(MYG1):​c.490-707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,200 control chromosomes in the GnomAD database, including 69,084 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 0.95 (69084 hom., cov: 32)
• Consequence: MYG1 NM_021640.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 1 publications found

Genes affected

MYG1 (HGNC:17590): (MYG1 exonuclease) Predicted to enable nuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Predicted to act upstream of or within locomotory exploration behavior. Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288663 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021640.4. 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
	MYG1	NM_021640.4	MANE Select	c.490-707A>G		intron	N/A	NP_067653.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYG1	ENST00000267103.10	TSL:1 MANE Select	c.490-707A>G		intron	N/A	ENSP00000267103.5
	MYG1	ENST00000548632.5	TSL:1	c.418-997A>G		intron	N/A	ENSP00000450270.1
	MYG1	ENST00000548845.5	TSL:1	n.706-707A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144425 AN: 152082 Hom.: 69046 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.971

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

GnomAD4 genome AF: 0.950 AC: 144519 AN: 152200 Hom.: 69084 Cov.: 32 AF XY: 0.951 AC XY: 70766 AN XY: 74424

African (AFR) AF: 0.823 AC: 34133 AN: 41470

American (AMR) AF: 0.984 AC: 15047 AN: 15292

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5174

South Asian (SAS) AF: 0.999 AC: 4825 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10614 AN: 10614

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68002 AN: 68030

Other (OTH) AF: 0.971 AC: 2051 AN: 2112

Alfa AF: 0.983 Hom.: 83285

Bravo AF: 0.942

Asia WGS AF: 0.988 AC: 3433 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
DANN	Benign	0.58
PhyloP100		0.13
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: rs4325348; hg19: chr12-53698985;