Genetic Variant NM_012228.4:c.55C>T (chr10-23095663-C-T) – 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.55C>T(p.Arg19Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000398 in 1,255,210 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MSRB2
NM_012228.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.233

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=0.080056906).

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.55C>T	p.Arg19Trp	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.55C>T	p.Arg19Trp	missense	Exon 1 of 5	ENSP00000365693.3	Q9Y3D2
MSRB2	ENST00000900184.1		c.55C>T	p.Arg19Trp	missense	Exon 1 of 5	ENSP00000570243.1
MSRB2	ENST00000900183.1		c.55C>T	p.Arg19Trp	missense	Exon 1 of 5	ENSP00000570242.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148030

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000398

AC:

AN:

1255210

Hom.:

Cov.:

AF XY:

0.00000325

AC XY:

AN XY:

614964

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25450

American (AMR)

AF:

0.00

AC:

AN:

19404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19238

East Asian (EAS)

AF:

0.00

AC:

AN:

27524

South Asian (SAS)

AF:

0.00

AC:

AN:

61330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3556

European-Non Finnish (NFE)

AF:

0.00000393

AC:

AN:

1017098

Other (OTH)

AF:

0.0000194

AC:

AN:

51550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

148030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72102

African (AFR)

AF:

0.00

AC:

AN:

39650

American (AMR)

AF:

0.00

AC:

AN:

14906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

4924

South Asian (SAS)

AF:

0.00

AC:

AN:

4686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67096

Other (OTH)

AF:

0.00

AC:

AN:

2010

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.25

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.17

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.53

M_CAP

Benign

0.049

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.63

PhyloP100

0.23

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.92

REVEL

Benign

0.13

Sift

Benign

0.079

Sift4G

Benign

0.23

Polyphen

0.0010

Vest4

0.099

MutPred

0.42

Loss of disorder (P = 9e-04)

MVP

0.41

MPC

0.19

ClinPred

0.32

GERP RS

0.49

PromoterAI

-0.18

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.40

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over