12-65278795-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000355192.8(MSRB3):​c.27C>T​(p.Arg9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,571,350 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 3 hom. )

Consequence

MSRB3
ENST00000355192.8 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.30
Variant links:
Genes affected
MSRB3 (HGNC:27375): (methionine sulfoxide reductase B3) The protein encoded by this gene catalyzes the reduction of methionine sulfoxide to methionine. This enzyme acts as a monomer and requires zinc as a cofactor. Several transcript variants encoding two different isoforms have been found for this gene. One of the isoforms localizes to mitochondria while the other localizes to endoplasmic reticula. [provided by RefSeq, Jul 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 12-65278795-C-T is Benign according to our data. Variant chr12-65278795-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1210517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65278795-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.3 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000151 (23/152034) while in subpopulation SAS AF= 0.00104 (5/4824). AF 95% confidence interval is 0.000408. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MSRB3NM_001031679.3 linkuse as main transcriptc.-122C>T 5_prime_UTR_variant 1/7 ENST00000308259.10 NP_001026849.1
MSRB3NM_198080.4 linkuse as main transcriptc.27C>T p.Arg9= synonymous_variant 1/6 NP_932346.1
MSRB3NM_001193460.2 linkuse as main transcriptc.-286C>T 5_prime_UTR_variant 1/8 NP_001180389.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MSRB3ENST00000308259.10 linkuse as main transcriptc.-122C>T 5_prime_UTR_variant 1/71 NM_001031679.3 ENSP00000312274 P1Q8IXL7-2

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
151918
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000727
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000455
AC:
82
AN:
180080
Hom.:
0
AF XY:
0.000571
AC XY:
55
AN XY:
96402
show subpopulations
Gnomad AFR exome
AF:
0.0000998
Gnomad AMR exome
AF:
0.000655
Gnomad ASJ exome
AF:
0.000114
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00177
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000174
Gnomad OTH exome
AF:
0.00123
GnomAD4 exome
AF:
0.000236
AC:
335
AN:
1419316
Hom.:
3
Cov.:
31
AF XY:
0.000279
AC XY:
196
AN XY:
702042
show subpopulations
Gnomad4 AFR exome
AF:
0.000155
Gnomad4 AMR exome
AF:
0.000854
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00196
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000907
Gnomad4 OTH exome
AF:
0.000323
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152034
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.0000725
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000308
Hom.:
0
Bravo
AF:
0.000215

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 22, 2024- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022MSRB3: BP4, BP7 -
Likely benign, criteria provided, single submitterclinical testingGeneDxNov 02, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
CADD
Benign
18
DANN
Benign
0.96

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373497233; hg19: chr12-65672575; API