rs891281233

Variant names:

• chr8-10054556-C-G
• rs891281233
• NM_012331.5:c.40C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-10054556-C-G
• chr8-10054556-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012331.5(MSRA):​c.40C>G​(p.Leu14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,435,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. L14F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MSRA NM_012331.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463
• 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]

MSRA-DT (HGNC:55400): (MSRA divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038177073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.40C>G	p.Leu14Val	missense_variant	Exon 1 of 6	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.40C>G	p.Leu14Val	missense_variant	Exon 1 of 6	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1435068 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 713888

African (AFR) AF: 0.0000650 AC: 2 AN: 30760

American (AMR) AF: 0.00 AC: 0 AN: 42032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25336

East Asian (EAS) AF: 0.00 AC: 0 AN: 35958

South Asian (SAS) AF: 0.00 AC: 0 AN: 83968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099158

Other (OTH) AF: 0.00 AC: 0 AN: 59314

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	1.2
DANN	Benign	0.52
DEOGEN2	Benign	0.17	T;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.038	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;.
PhyloP100		-0.46
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.0	N;N;N
REVEL	Benign	0.022
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.28
MutPred		0.32		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.061
MPC		0.0017
ClinPred		0.084	T
GERP RS		-0.32
PromoterAI		0.059	Neutral
Varity_R		0.066
gMVP		0.29
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs891281233; hg19: chr8-9912066;