16-1943116-T-C

Position:

chr16-1943116-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016332.4(MSRB1):c.41A>G(p.Asn14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,560,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

MSRB1
NM_016332.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

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:

LOC124903625 (HGNC:):

LOC124903625 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.090783566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRB1	NM_016332.4 linkuse as main transcript	c.41A>G	p.Asn14Ser	missense_variant	1/4	ENST00000361871.8	NP_057416.1	Q9NZV6
MSRB1	NM_001382264.1 linkuse as main transcript	c.41A>G	p.Asn14Ser	missense_variant	1/4		NP_001369193.1
MSRB1	NM_001382265.1 linkuse as main transcript	c.41A>G	p.Asn14Ser	missense_variant	1/3		NP_001369194.1
LOC124903625	XR_007064940.1 linkuse as main transcript	n.220T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MSRB1	ENST00000361871.8 linkuse as main transcript	c.41A>G	p.Asn14Ser	missense_variant	1/4	1	NM_016332.4	ENSP00000355084.3	Q9NZV6
MSRB1	ENST00000399753.2 linkuse as main transcript	c.41A>G	p.Asn14Ser	missense_variant	1/3	3		ENSP00000382657.2	A8MYR2
MSRB1	ENST00000564908.1 linkuse as main transcript	c.41A>G	p.Asn14Ser	missense_variant	1/5	3		ENSP00000456557.1	H3BS64
MSRB1	ENST00000473663.1 linkuse as main transcript	c.7A>G	p.Ile3Val	missense_variant	1/3	5		ENSP00000457320.1	H3BTT6

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

167348

Hom.:

AF XY:

0.0000112

AC XY:

AN XY:

89674

show subpopulations

Gnomad AFR exome

AF:

0.000448

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000994

AC:

AN:

1408930

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

696014

show subpopulations

Gnomad4 AFR exome

AF:

0.000344

Gnomad4 AMR exome

AF:

0.0000267

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000342

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152000

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.000242

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000263

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000260

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2023

The c.41A>G (p.N14S) alteration is located in exon 1 (coding exon 1) of the MSRB1 gene. This alteration results from a A to G substitution at nucleotide position 41, causing the asparagine (N) at amino acid position 14 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T;.;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.091

T;T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.91

L;.;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

N;.;N;N

REVEL

Benign

0.27

Sift

Benign

0.043

D;.;D;D

Sift4G

Benign

0.13

T;T;D;D

Polyphen

0.087

B;.;.;.

Vest4

0.20

MVP

0.50

MPC

0.11

ClinPred

0.043

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over