NM_016332.4:c.14G>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_016332.4(MSRB1):c.14G>T(p.Ser5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,409,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S5T) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
MSRB1
NM_016332.4 missense
NM_016332.4 missense
Scores
3
13
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.28
Publications
0 publications found
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]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
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
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MSRB1 | NM_016332.4 | MANE Select | c.14G>T | p.Ser5Ile | missense | Exon 1 of 4 | NP_057416.1 | Q9NZV6 | |
| MSRB1 | NM_001382264.1 | c.14G>T | p.Ser5Ile | missense | Exon 1 of 4 | NP_001369193.1 | |||
| MSRB1 | NM_001382265.1 | c.14G>T | p.Ser5Ile | missense | Exon 1 of 3 | NP_001369194.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MSRB1 | ENST00000361871.8 | TSL:1 MANE Select | c.14G>T | p.Ser5Ile | missense | Exon 1 of 4 | ENSP00000355084.3 | Q9NZV6 | |
| MSRB1 | ENST00000564908.1 | TSL:3 | c.14G>T | p.Ser5Ile | missense | Exon 1 of 5 | ENSP00000456557.1 | H3BS64 | |
| MSRB1 | ENST00000399753.3 | n.53G>T | non_coding_transcript_exon | Exon 1 of 3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 7.09e-7 AC: 1AN: 1409848Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1AN XY: 696648 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1409848
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
696648
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
31988
American (AMR)
AF:
AC:
0
AN:
37620
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25286
East Asian (EAS)
AF:
AC:
0
AN:
36478
South Asian (SAS)
AF:
AC:
0
AN:
80056
European-Finnish (FIN)
AF:
AC:
0
AN:
49106
Middle Eastern (MID)
AF:
AC:
0
AN:
5716
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1085166
Other (OTH)
AF:
AC:
0
AN:
58432
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Loss of disorder (P = 0.001)
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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