NM_016332.4:c.22G>C

Variant names:

• chr16-1943135-C-G
• rs1293200994
• NM_016332.4:c.22G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016332.4(MSRB1):​c.22G>C​(p.Gly8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,410,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MSRB1 NM_016332.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.906
• 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]

LOC124903625 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29607815).

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.22G>C	p.Gly8Arg	missense	Exon 1 of 4	NP_057416.1	Q9NZV6
	MSRB1	NM_001382264.1		c.22G>C	p.Gly8Arg	missense	Exon 1 of 4	NP_001369193.1
	MSRB1	NM_001382265.1		c.22G>C	p.Gly8Arg	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.22G>C	p.Gly8Arg	missense	Exon 1 of 4	ENSP00000355084.3	Q9NZV6
	MSRB1	ENST00000564908.1	TSL:3	c.22G>C	p.Gly8Arg	missense	Exon 1 of 5	ENSP00000456557.1	H3BS64
	MSRB1	ENST00000399753.3		n.61G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 169880 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1410576 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 696950

African (AFR) AF: 0.00 AC: 0 AN: 32022

American (AMR) AF: 0.00 AC: 0 AN: 37720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25282

East Asian (EAS) AF: 0.00 AC: 0 AN: 36548

South Asian (SAS) AF: 0.00 AC: 0 AN: 80096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1085556

Other (OTH) AF: 0.00 AC: 0 AN: 58456

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.095
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.91
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.49
Sift	Benign	0.067	T
Sift4G	Uncertain	0.054	T
Polyphen		0.43	B
Vest4		0.27
MutPred		0.53		Loss of sheet (P = 0.0457)
MVP		0.58
MPC		0.21
ClinPred		0.94	D
GERP RS		3.1
PromoterAI		0.52	Over-expression
Varity_R		0.29

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

Other links and lift over

dbSNP: rs1293200994; hg19: chr16-1993136;