NM_016332.4:c.22G>A

Variant names:

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

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>A​(p.Gly8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSRB1 NM_016332.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.29884127).

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1410576 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 1085556

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

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	-0.10
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.91
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.50
Sift	Benign	0.067	T
Sift4G	Uncertain	0.054	T
Polyphen		0.62	P
Vest4		0.27
MutPred		0.53		Loss of sheet (P = 0.0457)
MVP		0.58
MPC		0.21
ClinPred		0.95	D
GERP RS		3.1
PromoterAI		-0.079	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;