chr8-10209897-G-A

Variant names:

• chr8-10209897-G-A
• rs6992349
• NM_012331.5:c.211+1996G>A

Variant summary

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

The NM_012331.5(MSRA):​c.211+1996G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,186 control chromosomes in the GnomAD database, including 10,752 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 0.34 (10752 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012331.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	NM_012331.5	MANE Select	c.211+1996G>A		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.211+1996G>A		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.82+1996G>A		intron	N/A	NP_001129143.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	ENST00000317173.9	TSL:1 MANE Select	c.211+1996G>A		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.82+1996G>A		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.13+1996G>A		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51399 AN: 152068 Hom.: 10710 Cov.: 33

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.338 AC: 51504 AN: 152186 Hom.: 10752 Cov.: 33 AF XY: 0.337 AC XY: 25056 AN XY: 74418

African (AFR) AF: 0.595 AC: 24684 AN: 41492

American (AMR) AF: 0.269 AC: 4117 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 783 AN: 3462

East Asian (EAS) AF: 0.221 AC: 1143 AN: 5180

South Asian (SAS) AF: 0.412 AC: 1988 AN: 4826

European-Finnish (FIN) AF: 0.205 AC: 2176 AN: 10596

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15736 AN: 68012

Other (OTH) AF: 0.304 AC: 644 AN: 2116

Alfa AF: 0.192 Hom.: 578

Bravo AF: 0.349

Asia WGS AF: 0.380 AC: 1319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.48
PhyloP100		-0.11
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: rs6992349; hg19: chr8-10067407;