12-53305709-C-G

Variant names:

• chr12-53305709-C-G
• rs2279025
• NM_021640.4:c.490-199C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_021640.4(MYG1):​c.490-199C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000638 in 597,528 control chromosomes in the GnomAD database, including 4 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 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (4 hom.)
• Consequence: MYG1 NM_021640.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYG1	NM_021640.4	c.490-199C>G		intron_variant	Intron 3 of 6	ENST00000267103.10	NP_067653.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYG1	ENST00000267103.10	c.490-199C>G		intron_variant	Intron 3 of 6	1	NM_021640.4	ENSP00000267103.5

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000728 AC: 324 AN: 445224 Hom.: 4 Cov.: 6 AF XY: 0.000667 AC XY: 153 AN XY: 229356

African (AFR) AF: 0.00 AC: 0 AN: 11740

American (AMR) AF: 0.00 AC: 0 AN: 11980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12268

East Asian (EAS) AF: 0.0118 AC: 311 AN: 26274

South Asian (SAS) AF: 0.000321 AC: 11 AN: 34244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1864

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 296140

Other (OTH) AF: 0.0000822 AC: 2 AN: 24328

GnomAD4 genome AF: 0.000374 AC: 57 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000442

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.75
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism

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: rs2279025; hg19: chr12-53699493;