Genetic Variant MSRB2:p.Arg3Gly (chr10-23095615-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012228.4(MSRB2):c.7C>G(p.Arg3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000227 in 1,324,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

MSRB2
NM_012228.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.275

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09670612).

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.7C>G	p.Arg3Gly	missense	Exon 1 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.7C>G	p.Arg3Gly	missense	Exon 1 of 5	ENSP00000365693.3	Q9Y3D2
MSRB2	ENST00000900184.1		c.7C>G	p.Arg3Gly	missense	Exon 1 of 5	ENSP00000570243.1
MSRB2	ENST00000900183.1		c.7C>G	p.Arg3Gly	missense	Exon 1 of 5	ENSP00000570242.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000227

AC:

AN:

1324248

Hom.:

Cov.:

AF XY:

0.00000306

AC XY:

AN XY:

652846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26906

American (AMR)

AF:

0.00

AC:

AN:

28734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22986

East Asian (EAS)

AF:

0.00

AC:

AN:

28470

South Asian (SAS)

AF:

0.00

AC:

AN:

74212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3932

European-Non Finnish (NFE)

AF:

0.00000285

AC:

AN:

1051592

Other (OTH)

AF:

0.00

AC:

AN:

54792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.17

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.27

M_CAP

Benign

0.066

MetaRNN

Benign

0.097

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.0

PhyloP100

-0.28

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.66

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.054

Vest4

0.17

MutPred

0.48

Loss of stability (P = 0.0343)

MVP

0.45

MPC

0.24

ClinPred

0.58

GERP RS

0.59

PromoterAI

-0.0088

Neutral

(source)

Varity_R

0.26

gMVP

0.65

Mutation Taster

=93/7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over