NM_016332.4:c.58G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_016332.4(MSRB1):c.58G>A(p.Val20Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,610,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

MSRB1
NM_016332.4 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.234

Publications

1 publications found

Variant links:

Genes affected

MSRB1 (HGNC:14133): (methionine sulfoxide reductase B1) The protein encoded by this gene belongs to the methionine-R-sulfoxide reductase B (MsrB) family. Members of this family function as repair enzymes that protect proteins from oxidative stress by catalyzing the reduction of methionine-R-sulfoxides to methionines. This protein is highly expressed in liver and kidney, and is localized to the nucleus and cytosol. It is the only member of the MsrB family that is a selenoprotein, containing a selenocysteine (Sec) residue at its active site. It also has the highest methionine-R-sulfoxide reductase activity compared to other members containing cysteine in place of Sec. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. A pseudogene of this locus has been identified on chromosome 19. [provided by RefSeq, Aug 2017]

MSRB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028415889).

BP6

Variant 16-1941403-C-T is Benign according to our data. Variant chr16-1941403-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2383101.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016332.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSRB1	NM_016332.4	MANE Select	c.58G>A	p.Val20Ile	missense splice_region	Exon 2 of 4	NP_057416.1	Q9NZV6
MSRB1	NM_001382264.1		c.58G>A	p.Val20Ile	missense splice_region	Exon 2 of 4	NP_001369193.1
MSRB1	NM_001382265.1		c.58G>A	p.Val20Ile	missense splice_region	Exon 2 of 3	NP_001369194.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSRB1	ENST00000361871.8	TSL:1 MANE Select	c.58G>A	p.Val20Ile	missense splice_region	Exon 2 of 4	ENSP00000355084.3	Q9NZV6
MSRB1	ENST00000564908.1	TSL:3	c.58G>A	p.Val20Ile	missense splice_region	Exon 2 of 5	ENSP00000456557.1	H3BS64
MSRB1	ENST00000473663.1	TSL:5	c.24G>A	p.Ala8Ala	splice_region synonymous	Exon 2 of 3	ENSP00000457320.1	H3BTT6

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000206

AC:

AN:

242526

AF XY:

0.0000227

show subpopulations

Gnomad AFR exome

AF:

0.0000667

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1458206

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

725094

show subpopulations

African (AFR)

AF:

0.000510

AC:

AN:

33366

American (AMR)

AF:

0.00

AC:

AN:

44198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25966

East Asian (EAS)

AF:

0.00

AC:

AN:

39612

South Asian (SAS)

AF:

0.0000349

AC:

AN:

85868

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53010

Middle Eastern (MID)

AF:

0.000696

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1110208

Other (OTH)

AF:

0.0000996

AC:

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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

AF:

0.0000394

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41434

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00316

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000331

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.070

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.021

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.13

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.64

M_CAP

Benign

0.073

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.61

PhyloP100

-0.23

PrimateAI

Benign

0.40

PROVEAN

Benign

0.13

REVEL

Benign

0.20

Sift

Benign

0.91

Sift4G

Benign

0.92

Polyphen

0.0

Vest4

0.13

MutPred

0.45

Gain of methylation at K25 (P = 0.089)

MVP

0.13

MPC

0.11

ClinPred

0.041

GERP RS

-6.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.038

Mutation Taster

=87/13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over