NM_012228.4:c.55C>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012228.4(MSRB2):​c.55C>A​(p.Arg19Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000797 in 1,255,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: MSRB2 NM_012228.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.233 with no splicing effect.

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>A	p.Arg19Arg	synonymous	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>A	p.Arg19Arg	synonymous	Exon 1 of 5	ENSP00000365693.3	Q9Y3D2
	MSRB2	ENST00000900184.1		c.55C>A	p.Arg19Arg	synonymous	Exon 1 of 5	ENSP00000570243.1
	MSRB2	ENST00000900183.1		c.55C>A	p.Arg19Arg	synonymous	Exon 1 of 5	ENSP00000570242.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.97e-7 AC: 1 AN: 1255210 Hom.: 0 Cov.: 31 AF XY: 0.00000163 AC XY: 1 AN XY: 614964

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.0000163 AC: 1 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: 0.00 AC: 0 AN: 1017098

Other (OTH) AF: 0.00 AC: 0 AN: 51550

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.3
DANN	Benign	0.74
PhyloP100		0.23
PromoterAI		-0.077	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;