16-1943143-C-A

Variant names:

• chr16-1943143-C-A
• NM_016332.4:c.14G>T

Variant summary

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

The NM_016332.4(MSRB1):​c.14G>T​(p.Ser5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,409,848 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MSRB1 NM_016332.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRB1	NM_016332.4	c.14G>T	p.Ser5Ile	missense_variant	Exon 1 of 4	ENST00000361871.8	NP_057416.1
MSRB1	NM_001382264.1	c.14G>T	p.Ser5Ile	missense_variant	Exon 1 of 4		NP_001369193.1
MSRB1	NM_001382265.1	c.14G>T	p.Ser5Ile	missense_variant	Exon 1 of 3		NP_001369194.1
LOC124903625	XR_007064940.1	n.247C>A		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.14G>T	p.Ser5Ile	missense_variant	Exon 1 of 4	1	NM_016332.4	ENSP00000355084.3
MSRB1	ENST00000399753.2	c.14G>T	p.Ser5Ile	missense_variant	Exon 1 of 3	3		ENSP00000382657.2
MSRB1	ENST00000564908.1	c.14G>T	p.Ser5Ile	missense_variant	Exon 1 of 5	3		ENSP00000456557.1
MSRB1	ENST00000473663.1	c.-21G>T		upstream_gene_variant		5		ENSP00000457320.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1409848 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 696648

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: 9.22e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T;T;.;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Uncertain	-0.099	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.4	D;.;D;N
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0030	D;.;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.83	P;.;.;.
Vest4		0.50
MutPred		0.70		Loss of disorder (P = 0.001);Loss of disorder (P = 0.001);Loss of disorder (P = 0.001);Loss of disorder (P = 0.001);
MVP		0.69
MPC		0.44
ClinPred		0.89	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-1993144;