Genetic Variant NM_012228.4:c.196A>G (chr10-23104221-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_012228.4(MSRB2):c.196A>G(p.Thr66Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0013 in 1,613,704 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

MSRB2
NM_012228.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.32

Publications

5 publications found

Variant links:

Genes affected

MSRB2 (HGNC:17061): (methionine sulfoxide reductase B2) Predicted to enable actin binding activity; peptide-methionine (R)-S-oxide reductase activity; and zinc ion binding activity. Predicted to be involved in actin filament polymerization and protein repair. Predicted to be located in mitochondrion. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MSRB2 links:

ENSG00000286924 (HGNC:):

ENSG00000286924 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07840693).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012228.4. 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
	MSRB2	NM_012228.4	MANE Select	c.196A>G	p.Thr66Ala	missense	Exon 2 of 5	NP_036360.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSRB2	ENST00000376510.8	TSL:1 MANE Select	c.196A>G	p.Thr66Ala	missense	Exon 2 of 5	ENSP00000365693.3	Q9Y3D2
MSRB2	ENST00000900184.1		c.196A>G	p.Thr66Ala	missense	Exon 2 of 5	ENSP00000570243.1
MSRB2	ENST00000900183.1		c.196A>G	p.Thr66Ala	missense	Exon 2 of 5	ENSP00000570242.1

Frequencies

GnomAD3 genomes

AF:

0.000959

AC:

146

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000984

AC:

244

AN:

247968

AF XY:

0.000973

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.00169

Gnomad OTH exome

AF:

0.000832

GnomAD4 exome

AF:

0.00134

AC:

1951

AN:

1461352

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

897

AN XY:

727002

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33444

American (AMR)

AF:

0.00110

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00165

AC:

1831

AN:

1111786

Other (OTH)

AF:

0.000961

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

178

268

357

446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

124

186

248

310

<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:

0.000958

AC:

146

AN:

152352

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41578

American (AMR)

AF:

0.00137

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00151

AC:

103

AN:

68024

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00151

Hom.:

Bravo

AF:

0.00102

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000775

AC:

ESP6500EA

AF:

0.00181

AC:

ExAC

AF:

0.000935

AC:

113

EpiCase

AF:

0.00214

EpiControl

AF:

0.00190

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

Eigen

Benign

0.12

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.037

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.7

PhyloP100

5.3

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.44

Sift

Benign

0.18

Sift4G

Benign

0.19

Polyphen

0.38

Vest4

0.50

MVP

0.82

MPC

0.66

ClinPred

0.048

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.15

gMVP

0.64

Mutation Taster

=94/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over