16-1943135-C-T

Variant names:

• chr16-1943135-C-T
• rs1293200994
• NM_016332.4:c.22G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016332.4(MSRB1):​c.22G>A​(p.Gly8Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSRB1 NM_016332.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906

Genes affected

MSRB1 (HGNC:14133): (methionine sulfoxide reductase B1) The protein encoded by this gene belongs to the methionine-R-sulfoxide reductase B (MsrB) family. Members of this family function as repair enzymes that protect proteins from oxidative stress by catalyzing the reduction of methionine-R-sulfoxides to methionines. This protein is highly expressed in liver and kidney, and is localized to the nucleus and cytosol. It is the only member of the MsrB family that is a selenoprotein, containing a selenocysteine (Sec) residue at its active site. It also has the highest methionine-R-sulfoxide reductase activity compared to other members containing cysteine in place of Sec. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. A pseudogene of this locus has been identified on chromosome 19. [provided by RefSeq, Aug 2017]

LOC124903625 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29884127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRB1	NM_016332.4	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 4	ENST00000361871.8	NP_057416.1
MSRB1	NM_001382264.1	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 4		NP_001369193.1
MSRB1	NM_001382265.1	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 3		NP_001369194.1
LOC124903625	XR_007064940.1	n.239C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRB1	ENST00000361871.8	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 4	1	NM_016332.4	ENSP00000355084.3
MSRB1	ENST00000399753.2	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 3	3		ENSP00000382657.2
MSRB1	ENST00000564908.1	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 5	3		ENSP00000456557.1
MSRB1	ENST00000473663.1	c.-13G>A		upstream_gene_variant		5		ENSP00000457320.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1410576 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 696950

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.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T;.;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.4	M;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.3	D;.;D;D
REVEL	Uncertain	0.50
Sift	Benign	0.067	T;.;D;D
Sift4G	Uncertain	0.054	T;T;D;D
Polyphen		0.62	P;.;.;.
Vest4		0.27
MutPred		0.53		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.58
MPC		0.21
ClinPred		0.95	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		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

LitVar

Other links and lift over

dbSNP: rs1293200994; hg19: chr16-1993136;