10-23095721-A-G

Position:

• chr10-23095721-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012228.4(MSRB2):​c.113A>G​(p.Glu38Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSRB2 NM_012228.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.298

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08886713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRB2	NM_012228.4	c.113A>G	p.Glu38Gly	missense_variant	1/5	ENST00000376510.8
MSRB2	XM_011519426.3	c.113A>G	p.Glu38Gly	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRB2	ENST00000376510.8	c.113A>G	p.Glu38Gly	missense_variant	1/5	1	NM_012228.4	P1
	ENST00000655462.1	n.116+37968T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1107662 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 528472

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 21, 2021

The c.113A>G (p.E38G) alteration is located in exon 1 (coding exon 1) of the MSRB2 gene. This alteration results from a A to G substitution at nucleotide position 113, causing the glutamic acid (E) at amino acid position 38 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.044
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.033	D
Polyphen		0.024	B
Vest4		0.075
MutPred		0.23		Loss of solvent accessibility (P = 0.0299);
MVP		0.49
MPC		0.22
ClinPred		0.26	T
GERP RS		1.4
Varity_R		0.066
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs911851386; hg19: chr10-23384650; COSMIC: COSV64737340;