NM_012228.4:c.92G>C

Variant names:

• chr10-23095700-G-C
• rs2131618252
• NM_012228.4:c.92G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012228.4(MSRB2):​c.92G>C​(p.Gly31Ala) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G31C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MSRB2 NM_012228.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.723
• Publications: 0 publications found

Genes affected

MSRB2 (HGNC:17061): (methionine sulfoxide reductase B2) Predicted to enable actin binding activity; peptide-methionine (R)-S-oxide reductase activity; and zinc ion binding activity. Predicted to be involved in actin filament polymerization and protein repair. Predicted to be located in mitochondrion. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286924 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07004237).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012228.4. 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
	MSRB2	NM_012228.4	MANE Select	c.92G>C	p.Gly31Ala	missense	Exon 1 of 5	NP_036360.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRB2	ENST00000376510.8	TSL:1 MANE Select	c.92G>C	p.Gly31Ala	missense	Exon 1 of 5	ENSP00000365693.3	Q9Y3D2
	MSRB2	ENST00000900184.1		c.92G>C	p.Gly31Ala	missense	Exon 1 of 5	ENSP00000570243.1
	MSRB2	ENST00000900183.1		c.92G>C	p.Gly31Ala	missense	Exon 1 of 5	ENSP00000570242.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

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	0.077
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.3
DANN	Benign	0.37
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.72
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.033
Sift	Benign	0.69	T
Sift4G	Benign	0.78	T
Polyphen		0.013	B
Vest4		0.18
MutPred		0.24		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.22
MPC		0.20
ClinPred		0.042	T
GERP RS		0.49
PromoterAI		-0.029	Neutral
Varity_R		0.050
gMVP		0.29
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs2131618252; hg19: chr10-23384629;