Variant chr12-53306208-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021640.4(MYG1):c.653A>G(p.Lys218Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

MYG1
NM_021640.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Variant links:

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]

MYG1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044225782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYG1	NM_021640.4 linkuse as main transcript	c.653A>G	p.Lys218Arg	missense_variant	5/7	ENST00000267103.10	NP_067653.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYG1	ENST00000267103.10 linkuse as main transcript	c.653A>G	p.Lys218Arg	missense_variant	5/7	1	NM_021640.4	ENSP00000267103	P1

Frequencies

GnomAD3 genomes

AF:

0.000236

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000195

AC:

AN:

251464

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000360

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000270

AC:

394

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

189

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.000334

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000236

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000299

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.653A>G (p.K218R) alteration is located in exon 5 (coding exon 5) of the C12orf10 gene. This alteration results from a A to G substitution at nucleotide position 653, causing the lysine (K) at amino acid position 218 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.070

T;T;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.044

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.10

N;.;.

MutationTaster

Benign

0.66

N;N;N

PROVEAN

Benign

-0.52

N;N;N

REVEL

Benign

0.030

Sift

Benign

0.46

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.12

MVP

0.25

MPC

0.12

ClinPred

0.051

GERP RS

0.59

Varity_R

0.062

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over