dbSNP rs1534283: MYG1:p.Gln4His (chr12-53299749-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021640.4(MYG1):c.12A>C(p.Gln4His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,613,064 control chromosomes in the GnomAD database, including 792,202 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 ( 68967 hom., cov: 31)

Exomes 𝑓: 0.99 ( 723235 hom. )

Consequence

MYG1
NM_021640.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.15

Publications

25 publications found

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:

ENSG00000288663 (HGNC:):

ENSG00000288663 links:

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

MYG1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=1.2454103E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYG1	NM_021640.4 link	c.12A>C	p.Gln4His	missense_variant	Exon 1 of 7	ENST00000267103.10	NP_067653.4	Q9HB07

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYG1	ENST00000267103.10 link	c.12A>C	p.Gln4His	missense_variant	Exon 1 of 7	1	NM_021640.4	ENSP00000267103.5		Q9HB07

Frequencies

GnomAD3 genomes

AF:

0.950

AC:

144198

AN:

151860

Hom.:

68929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.823

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.984

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.998

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.990

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.971

GnomAD2 exomes

AF:

0.987

AC:

244228

AN:

247402

AF XY:

0.991

show subpopulations

Gnomad AFR exome

AF:

0.817

Gnomad AMR exome

AF:

0.993

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.995

GnomAD4 exome

AF:

0.995

AC:

1453143

AN:

1461086

Hom.:

723235

Cov.:

AF XY:

0.995

AC XY:

723466

AN XY:

726848

show subpopulations

African (AFR)

AF:

0.806

AC:

26945

AN:

33432

American (AMR)

AF:

0.991

AC:

44262

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26101

AN:

26102

East Asian (EAS)

AF:

1.00

AC:

39660

AN:

39668

South Asian (SAS)

AF:

1.00

AC:

86155

AN:

86192

European-Finnish (FIN)

AF:

1.00

AC:

53260

AN:

53260

Middle Eastern (MID)

AF:

0.992

AC:

5646

AN:

5694

European-Non Finnish (NFE)

AF:

1.00

AC:

1111470

AN:

1111742

Other (OTH)

AF:

0.988

AC:

59644

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

370

740

1109

1479

1849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21656

43312

64968

86624

108280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.949

AC:

144292

AN:

151978

Hom.:

68967

Cov.:

AF XY:

0.951

AC XY:

70657

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.822

AC:

33994

AN:

41334

American (AMR)

AF:

0.984

AC:

15042

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3464

AN:

3464

East Asian (EAS)

AF:

0.999

AC:

5139

AN:

5142

South Asian (SAS)

AF:

0.999

AC:

4826

AN:

4832

European-Finnish (FIN)

AF:

1.00

AC:

10624

AN:

10624

Middle Eastern (MID)

AF:

0.990

AC:

289

AN:

292

European-Non Finnish (NFE)

AF:

1.00

AC:

67951

AN:

67980

Other (OTH)

AF:

0.971

AC:

2051

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

318

636

955

1273

1591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.982

Hom.:

145901

Bravo

AF:

0.942

TwinsUK

AF:

1.00

AC:

3707

ALSPAC

AF:

0.999

AC:

3852

ESP6500AA

AF:

0.824

AC:

3629

ESP6500EA

AF:

1.00

AC:

8594

ExAC

AF:

0.983

AC:

119224

Asia WGS

AF:

0.988

AC:

3435

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

0.999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.8

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.053

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00050

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0000012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-2.2

PROVEAN

Benign

0.38

REVEL

Benign

0.026

Sift

Benign

0.11

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.027

MutPred

0.22

Gain of catalytic residue at M1 (P = 0.034);

MPC

0.14

ClinPred

0.0033

GERP RS

-4.5

PromoterAI

0.46

Neutral

(source)

Varity_R

0.053

gMVP

0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over