Genetic Variant MSRB2:p.Ser114Ser (chr10-23119349-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_012228.4(MSRB2):c.342C>T(p.Ser114Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,762 control chromosomes in the GnomAD database, including 85,085 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6597 hom., cov: 31)

Exomes 𝑓: 0.32 ( 78488 hom. )

Consequence

MSRB2
NM_012228.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.05

Publications

26 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=-3.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRB2	NM_012228.4 link	c.342C>T	p.Ser114Ser	synonymous_variant	Exon 4 of 5	ENST00000376510.8	NP_036360.3	Q9Y3D2
MSRB2	XM_011519426.3 link	c.*174C>T		3_prime_UTR_variant	Exon 4 of 4		XP_011517728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MSRB2	ENST00000376510.8 link	c.342C>T	p.Ser114Ser	synonymous_variant	Exon 4 of 5	1	NM_012228.4	ENSP00000365693.3	Q9Y3D2
MSRB2	ENST00000468633.1 link	n.206C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
MSRB2	ENST00000472663.1 link	n.311C>T		non_coding_transcript_exon_variant	Exon 4 of 5	5		ENSP00000434990.1	H0YE51
ENSG00000286924	ENST00000655462.1 link	n.116+14340G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.287

AC:

43603

AN:

151900

Hom.:

6593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.284

AC:

70945

AN:

249376

AF XY:

0.291

show subpopulations

Gnomad AFR exome

AF:

0.242

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.319

Gnomad EAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.339

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.324

AC:

473051

AN:

1461744

Hom.:

78488

Cov.:

AF XY:

0.324

AC XY:

235480

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.236

AC:

7889

AN:

33474

American (AMR)

AF:

0.176

AC:

7851

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

8354

AN:

26130

East Asian (EAS)

AF:

0.152

AC:

6038

AN:

39700

South Asian (SAS)

AF:

0.276

AC:

23769

AN:

86248

European-Finnish (FIN)

AF:

0.326

AC:

17426

AN:

53420

Middle Eastern (MID)

AF:

0.256

AC:

1475

AN:

5758

European-Non Finnish (NFE)

AF:

0.343

AC:

381379

AN:

1111904

Other (OTH)

AF:

0.312

AC:

18870

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

17041

34081

51122

68162

85203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.287

AC:

43625

AN:

152018

Hom.:

6597

Cov.:

AF XY:

0.282

AC XY:

20990

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.239

AC:

9895

AN:

41444

American (AMR)

AF:

0.213

AC:

3259

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

1100

AN:

3466

East Asian (EAS)

AF:

0.136

AC:

704

AN:

5170

South Asian (SAS)

AF:

0.257

AC:

1238

AN:

4808

European-Finnish (FIN)

AF:

0.318

AC:

3354

AN:

10560

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.342

AC:

23210

AN:

67960

Other (OTH)

AF:

0.261

AC:

550

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1558

3116

4673

6231

7789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.318

Hom.:

37684

Bravo

AF:

0.277

Asia WGS

AF:

0.205

AC:

711

AN:

3478

EpiCase

AF:

0.338

EpiControl

AF:

0.336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.9

(source)

DANN

Benign

0.82

PhyloP100

-3.0

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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10-23119349-C-T

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