8-10242659-C-T

Variant names:

• chr8-10242659-C-T
• rs6992153
• NM_012331.5:c.212-2445C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012331.5(MSRA):​c.212-2445C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,148 control chromosomes in the GnomAD database, including 43,957 homozygotes. 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: 𝑓 0.76 (43957 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.212-2445C>T		intron_variant	Intron 2 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.212-2445C>T		intron_variant	Intron 2 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115263 AN: 152030 Hom.: 43943 Cov.: 33

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.751

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.758 AC: 115324 AN: 152148 Hom.: 43957 Cov.: 33 AF XY: 0.758 AC XY: 56402 AN XY: 74396

African (AFR) AF: 0.705 AC: 29222 AN: 41478

American (AMR) AF: 0.800 AC: 12231 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2702 AN: 3470

East Asian (EAS) AF: 0.668 AC: 3452 AN: 5168

South Asian (SAS) AF: 0.599 AC: 2888 AN: 4824

European-Finnish (FIN) AF: 0.799 AC: 8465 AN: 10594

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.791 AC: 53791 AN: 68008

Other (OTH) AF: 0.746 AC: 1575 AN: 2110

Alfa AF: 0.768 Hom.: 23400

Bravo AF: 0.756

Asia WGS AF: 0.608 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.25
DANN	Benign	0.55
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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: rs6992153; hg19: chr8-10100169;