Genetic Variant NM_033054.3:c.1466T>C (chr7-44969742-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_033054.3(MYO1G):c.1466T>C(p.Met489Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,609,976 control chromosomes in the GnomAD database, including 590,159 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.88 ( 59002 hom., cov: 32)

Exomes 𝑓: 0.85 ( 531157 hom. )

Consequence

MYO1G
NM_033054.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.680

Publications

30 publications found

Variant links:

Genes affected

MYO1G (HGNC:13880): (myosin IG) MYO1G is a plasma membrane-associated class I myosin (see MIM 601478) that is abundant in T and B lymphocytes and mast cells (Pierce et al., 2001 [PubMed 11544309]; Patino-Lopez et al., 2010 [PubMed 20071333]).[supplied by OMIM, Jun 2010]

MYO1G links:

ENSG00000308366 (HGNC:):

ENSG00000308366 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=6.551202E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1G	NM_033054.3 link	c.1466T>C	p.Met489Thr	missense_variant	Exon 11 of 22	ENST00000258787.12	NP_149043.2	B0I1T2-1
MYO1G	XR_007060129.1 link	n.1520T>C		non_coding_transcript_exon_variant	Exon 11 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1G	ENST00000258787.12 link	c.1466T>C	p.Met489Thr	missense_variant	Exon 11 of 22	1	NM_033054.3	ENSP00000258787.7		B0I1T2-1

Frequencies

GnomAD3 genomes

AF:

0.880

AC:

133420

AN:

151598

Hom.:

58947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.966

Gnomad AMI

AF:

0.907

Gnomad AMR

AF:

0.847

Gnomad ASJ

AF:

0.822

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.859

Gnomad FIN

AF:

0.883

Gnomad MID

AF:

0.827

Gnomad NFE

AF:

0.838

Gnomad OTH

AF:

0.846

GnomAD2 exomes

AF:

0.868

AC:

216816

AN:

249864

AF XY:

0.863

show subpopulations

Gnomad AFR exome

AF:

0.969

Gnomad AMR exome

AF:

0.895

Gnomad ASJ exome

AF:

0.824

Gnomad EAS exome

AF:

0.909

Gnomad FIN exome

AF:

0.882

Gnomad NFE exome

AF:

0.841

Gnomad OTH exome

AF:

0.852

GnomAD4 exome

AF:

0.853

AC:

1243681

AN:

1458260

Hom.:

531157

Cov.:

AF XY:

0.852

AC XY:

617939

AN XY:

725412

show subpopulations

African (AFR)

AF:

0.969

AC:

32387

AN:

33414

American (AMR)

AF:

0.892

AC:

39855

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.822

AC:

21437

AN:

26076

East Asian (EAS)

AF:

0.923

AC:

36523

AN:

39588

South Asian (SAS)

AF:

0.862

AC:

74092

AN:

85912

European-Finnish (FIN)

AF:

0.882

AC:

46383

AN:

52602

Middle Eastern (MID)

AF:

0.837

AC:

3903

AN:

4662

European-Non Finnish (NFE)

AF:

0.844

AC:

937664

AN:

1111168

Other (OTH)

AF:

0.855

AC:

51437

AN:

60182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

10121

20242

30363

40484

50605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21162

42324

63486

84648

105810

<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:

0.880

AC:

133534

AN:

151716

Hom.:

59002

Cov.:

AF XY:

0.881

AC XY:

65354

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.966

AC:

40021

AN:

41446

American (AMR)

AF:

0.847

AC:

12928

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.822

AC:

2843

AN:

3460

East Asian (EAS)

AF:

0.910

AC:

4662

AN:

5122

South Asian (SAS)

AF:

0.859

AC:

4133

AN:

4812

European-Finnish (FIN)

AF:

0.883

AC:

9346

AN:

10584

Middle Eastern (MID)

AF:

0.821

AC:

238

AN:

290

European-Non Finnish (NFE)

AF:

0.838

AC:

56759

AN:

67720

Other (OTH)

AF:

0.845

AC:

1782

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

805

1610

2415

3220

4025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.855

Hom.:

143213

Bravo

AF:

0.887

TwinsUK

AF:

0.837

AC:

3103

ALSPAC

AF:

0.840

AC:

3237

ESP6500AA

AF:

0.963

AC:

4244

ESP6500EA

AF:

0.841

AC:

7230

ExAC

AF:

0.869

AC:

105422

Asia WGS

AF:

0.866

AC:

3010

AN:

3476

EpiCase

AF:

0.831

EpiControl

AF:

0.832

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.7

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.032

T;T

MetaRNN

Benign

6.6e-7

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.4

N;.

PhyloP100

0.68

PrimateAI

Benign

0.34

PROVEAN

Benign

1.0

N;.

REVEL

Benign

0.099

Sift

Benign

0.45

T;.

Sift4G

Benign

0.28

T;.

Polyphen

0.0

B;.

Vest4

0.024

MPC

0.40

ClinPred

0.00061

GERP RS

4.0

Varity_R

0.059

gMVP

0.093

Mutation Taster

=99/1

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