rs1839851446

Variant names:

• chr10-23095663-C-T
• rs1839851446
• NM_012228.4:c.55C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-23095663-C-T
• chr10-23095663-C-A

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.55C>T​(p.Arg19Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000398 in 1,255,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000040 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSRB2 NM_012228.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.233
• 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=0.080056906).

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.55C>T	p.Arg19Trp	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.55C>T	p.Arg19Trp	missense	Exon 1 of 5	ENSP00000365693.3	Q9Y3D2
	MSRB2	ENST00000900184.1		c.55C>T	p.Arg19Trp	missense	Exon 1 of 5	ENSP00000570243.1
	MSRB2	ENST00000900183.1		c.55C>T	p.Arg19Trp	missense	Exon 1 of 5	ENSP00000570242.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 148030 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome AF: 0.00000398 AC: 5 AN: 1255210 Hom.: 0 Cov.: 31 AF XY: 0.00000325 AC XY: 2 AN XY: 614964

African (AFR) AF: 0.00 AC: 0 AN: 25450

American (AMR) AF: 0.00 AC: 0 AN: 19404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19238

East Asian (EAS) AF: 0.00 AC: 0 AN: 27524

South Asian (SAS) AF: 0.00 AC: 0 AN: 61330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3556

European-Non Finnish (NFE) AF: 0.00000393 AC: 4 AN: 1017098

Other (OTH) AF: 0.0000194 AC: 1 AN: 51550

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 148030 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 72102

African (AFR) AF: 0.00 AC: 0 AN: 39650

American (AMR) AF: 0.00 AC: 0 AN: 14906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 4924

South Asian (SAS) AF: 0.00 AC: 0 AN: 4686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67096

Other (OTH) AF: 0.00 AC: 0 AN: 2010

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.63	N
PhyloP100		0.23
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.13
Sift	Benign	0.079	T
Sift4G	Benign	0.23	T
Polyphen		0.0010	B
Vest4		0.099
MutPred		0.42		Loss of disorder (P = 9e-04)
MVP		0.41
MPC		0.19
ClinPred		0.32	T
GERP RS		0.49
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.40
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1839851446; hg19: chr10-23384592;