12-53300705-C-T

Variant names:

• chr12-53300705-C-T
• rs4759054
• NM_021640.4:c.329+443C>T

Variant summary

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

The NM_021640.4(MYG1):​c.329+443C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 152,150 control chromosomes in the GnomAD database, including 65,298 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 0.92 (65298 hom., cov: 30)
• Consequence: MYG1 NM_021640.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 4 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:):

MYG1-AS1 (HGNC:54810): (MYG1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.979 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYG1	NM_021640.4	MANE Select	c.329+443C>T		intron	N/A	NP_067653.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYG1	ENST00000267103.10	TSL:1 MANE Select	c.329+443C>T		intron	N/A	ENSP00000267103.5	Q9HB07
	MYG1	ENST00000548632.5	TSL:1	c.257+443C>T		intron	N/A	ENSP00000450270.1	F8VQQ3
	MYG1	ENST00000548845.5	TSL:1	n.545+443C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140055 AN: 152032 Hom.: 65265 Cov.: 30

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.916

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.953

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

GnomAD4 genome AF: 0.921 AC: 140143 AN: 152150 Hom.: 65298 Cov.: 30 AF XY: 0.922 AC XY: 68616 AN XY: 74402

African (AFR) AF: 0.765 AC: 31683 AN: 41440

American (AMR) AF: 0.969 AC: 14808 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 3441 AN: 3472

East Asian (EAS) AF: 0.958 AC: 4963 AN: 5178

South Asian (SAS) AF: 0.917 AC: 4415 AN: 4816

European-Finnish (FIN) AF: 1.00 AC: 10619 AN: 10622

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.985 AC: 67019 AN: 68020

Other (OTH) AF: 0.953 AC: 2011 AN: 2110

Alfa AF: 0.919 Hom.: 6705

Bravo AF: 0.913

Asia WGS AF: 0.920 AC: 3202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.6
DANN	Benign	0.80
PhyloP100		-0.095
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: rs4759054; hg19: chr12-53694489;