10-23095702-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012228.4(MSRB2):c.94A>C(p.Thr32Pro) 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: 0.824

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06392494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRB2	NM_012228.4	c.94A>C	p.Thr32Pro	missense_variant	1/5	ENST00000376510.8
MSRB2	XM_011519426.3	c.94A>C	p.Thr32Pro	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRB2	ENST00000376510.8	c.94A>C	p.Thr32Pro	missense_variant	1/5	1	NM_012228.4	P1
	ENST00000655462.1	n.116+37987T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1154746 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 557616

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 20, 2021

The c.94A>C (p.T32P) alteration is located in exon 1 (coding exon 1) of the MSRB2 gene. This alteration results from a A to C substitution at nucleotide position 94, causing the threonine (T) at amino acid position 32 to be replaced by a proline (P). 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	0.050
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	7.1
Dann	Benign	0.41
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.076
Sift	Benign	0.26	T
Sift4G	Benign	0.36	T
Polyphen		0.013	B
Vest4		0.12
MutPred		0.18		Loss of phosphorylation at T32 (P = 0.0106);
MVP		0.15
MPC		0.24
ClinPred		0.067	T
GERP RS		0.17
Varity_R		0.086
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-23384631;