NM_012331.5:c.276A>C

Variant names:

• chr8-10245168-A-C
• rs1171413366
• NM_012331.5:c.276A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012331.5(MSRA):​c.276A>C​(p.Gln92His) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q92P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MSRA NM_012331.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

Genes affected

MSRA (HGNC:7377): (methionine sulfoxide reductase A) This gene encodes a ubiquitous and highly conserved protein that carries out the enzymatic reduction of methionine sulfoxide to methionine. Human and animal studies have shown the highest levels of expression in kidney and nervous tissue. The protein functions in the repair of oxidatively damaged proteins to restore biological activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40804324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.276A>C	p.Gln92His	missense_variant	Exon 3 of 6	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.276A>C	p.Gln92His	missense_variant	Exon 3 of 6	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;T;.;.;.;.
Eigen	Benign	0.0032
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.41	T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.0	M;.;.;.;.;.
PhyloP100		1.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.3	N;D;D;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.016	D;D;D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D;D
Polyphen		0.67	P;.;.;.;.;B
Vest4		0.43
MutPred		0.49		Loss of MoRF binding (P = 0.11);Loss of MoRF binding (P = 0.11);.;.;.;.;
MVP		0.10
MPC		0.0031
ClinPred		0.87	D
GERP RS		3.1
Varity_R		0.16
gMVP		0.52
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs1171413366; hg19: chr8-10102678;