10-23119349-C-T

Variant names:

• chr10-23119349-C-T
• rs7427
• NM_012228.4:c.342C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012228.4(MSRB2):​c.342C>T​(p.Ser114Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,762 control chromosomes in the GnomAD database, including 85,085 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S114S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.29 (6597 hom., cov: 31)
  • Exomes 𝑓: 0.32 (78488 hom.)
• Consequence: MSRB2 NM_012228.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.05
• Publications: 26 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-3.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

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.342C>T	p.Ser114Ser	synonymous	Exon 4 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.342C>T	p.Ser114Ser	synonymous	Exon 4 of 5	ENSP00000365693.3	Q9Y3D2
	MSRB2	ENST00000900184.1		c.369C>T	p.Ser123Ser	synonymous	Exon 4 of 5	ENSP00000570243.1
	MSRB2	ENST00000900183.1		c.363C>T	p.Ser121Ser	synonymous	Exon 4 of 5	ENSP00000570242.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43603 AN: 151900 Hom.: 6593 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.262

GnomAD2 exomes AF: 0.284 AC: 70945 AN: 249376 AF XY: 0.291

Gnomad AFR exome AF: 0.242

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.319

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.325

Gnomad NFE exome AF: 0.339

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.324 AC: 473051 AN: 1461744 Hom.: 78488 Cov.: 38 AF XY: 0.324 AC XY: 235480 AN XY: 727170

African (AFR) AF: 0.236 AC: 7889 AN: 33474

American (AMR) AF: 0.176 AC: 7851 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 8354 AN: 26130

East Asian (EAS) AF: 0.152 AC: 6038 AN: 39700

South Asian (SAS) AF: 0.276 AC: 23769 AN: 86248

European-Finnish (FIN) AF: 0.326 AC: 17426 AN: 53420

Middle Eastern (MID) AF: 0.256 AC: 1475 AN: 5758

European-Non Finnish (NFE) AF: 0.343 AC: 381379 AN: 1111904

Other (OTH) AF: 0.312 AC: 18870 AN: 60392

GnomAD4 genome AF: 0.287 AC: 43625 AN: 152018 Hom.: 6597 Cov.: 31 AF XY: 0.282 AC XY: 20990 AN XY: 74322

African (AFR) AF: 0.239 AC: 9895 AN: 41444

American (AMR) AF: 0.213 AC: 3259 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1100 AN: 3466

East Asian (EAS) AF: 0.136 AC: 704 AN: 5170

South Asian (SAS) AF: 0.257 AC: 1238 AN: 4808

European-Finnish (FIN) AF: 0.318 AC: 3354 AN: 10560

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23210 AN: 67960

Other (OTH) AF: 0.261 AC: 550 AN: 2108

Alfa AF: 0.318 Hom.: 37684

Bravo AF: 0.277

Asia WGS AF: 0.205 AC: 711 AN: 3478

EpiCase AF: 0.338

EpiControl AF: 0.336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.9
DANN	Benign	0.82
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs7427; hg19: chr10-23408278; COSMIC: COSV107500983;