chr10-23119349-C-T

Position:

• chr10-23119349-C-T

Variant summary

Our verdict is Benign. Variant got -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.

• 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

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]

MSRB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRB2	NM_012228.4	c.342C>T	p.Ser114Ser	synonymous_variant	4/5	ENST00000376510.8	NP_036360.3
MSRB2	XM_011519426.3	c.*174C>T		3_prime_UTR_variant	4/4		XP_011517728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRB2	ENST00000376510.8	c.342C>T	p.Ser114Ser	synonymous_variant	4/5	1	NM_012228.4	ENSP00000365693.3
MSRB2	ENST00000468633.1	n.206C>T		non_coding_transcript_exon_variant	1/2	2
MSRB2	ENST00000472663.1	n.311C>T		non_coding_transcript_exon_variant	4/5	5		ENSP00000434990.1
ENSG00000286924	ENST00000655462.1	n.116+14340G>A		intron_variant

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

GnomAD3 exomes AF: 0.284 AC: 70945 AN: 249376 Hom.: 10755 AF XY: 0.291 AC XY: 39320 AN XY: 135278

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 SAS exome AF: 0.273

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

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.312

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

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.261

Alfa AF: 0.323 Hom.: 19696

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.9
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs7427; hg19: chr10-23408278;