8-10242659-C-T

Position:

• chr8-10242659-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MSRA	NM_012331.5	c.212-2445C>T		intron_variant		ENST00000317173.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9	c.212-2445C>T		intron_variant		1	NM_012331.5	P1

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

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.746

Alfa AF: 0.766 Hom.: 21070

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

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

LitVar

Other links and lift over

dbSNP: rs6992153; hg19: chr8-10100169;