chr12-65278850-G-A

Position:

• chr12-65278850-G-A

Variant summary

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

The ENST00000308259.10(MSRB3):​c.-67G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,409,878 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: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MSRB3 ENST00000308259.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

Genes affected

MSRB3 (HGNC:27375): (methionine sulfoxide reductase B3) The protein encoded by this gene catalyzes the reduction of methionine sulfoxide to methionine. This enzyme acts as a monomer and requires zinc as a cofactor. Several transcript variants encoding two different isoforms have been found for this gene. One of the isoforms localizes to mitochondria while the other localizes to endoplasmic reticula. [provided by RefSeq, Jul 2010]

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=0.08577809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRB3	NM_001031679.3	c.-67G>A		5_prime_UTR_variant	1/7	ENST00000308259.10	NP_001026849.1
MSRB3	NM_198080.4	c.82G>A	p.Gly28Arg	missense_variant	1/6		NP_932346.1
MSRB3	NM_001193460.2	c.-231G>A		5_prime_UTR_variant	1/8		NP_001180389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRB3	ENST00000308259.10	c.-67G>A		5_prime_UTR_variant	1/7	1	NM_001031679.3	ENSP00000312274	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000599 AC: 1 AN: 166970 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 88432

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000151

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1409878 Hom.: 0 Cov.: 31 AF XY: 0.00000431 AC XY: 3 AN XY: 696350

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: 0.00000277

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000279 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.0000265 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.55	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.086	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Benign	0.32	N;N
REVEL	Benign	0.14
Sift	Benign	0.14	T;D
Sift4G	Benign	0.12	T;D
Polyphen		0.0010	B;.
Vest4		0.20
MutPred		0.35		Gain of catalytic residue at G33 (P = 0.0017);Gain of catalytic residue at G33 (P = 0.0017);
MVP		0.31
MPC		0.56
ClinPred		0.090	T
GERP RS		1.1
Varity_R		0.054
gMVP		0.32

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: rs368104588; hg19: chr12-65672630;