NM_012331.5:c.544-36178G>T

Variant names:

• chr8-10391970-G-T
• rs17765901
• NM_012331.5:c.544-36178G>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.544-36178G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,036 control chromosomes in the GnomAD database, including 12,914 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 0.39 (12914 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 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.544-36178G>T		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.424-36178G>T		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.415-36178G>T		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.544-36178G>T		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.415-36178G>T		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.346-36178G>T		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59822 AN: 151916 Hom.: 12911 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.0409

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.394 AC: 59834 AN: 152036 Hom.: 12914 Cov.: 32 AF XY: 0.384 AC XY: 28505 AN XY: 74302

African (AFR) AF: 0.287 AC: 11908 AN: 41480

American (AMR) AF: 0.311 AC: 4747 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1953 AN: 3468

East Asian (EAS) AF: 0.0408 AC: 211 AN: 5176

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4814

European-Finnish (FIN) AF: 0.390 AC: 4108 AN: 10546

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.497 AC: 33792 AN: 67962

Other (OTH) AF: 0.410 AC: 864 AN: 2108

Alfa AF: 0.463 Hom.: 70368

Bravo AF: 0.378

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.67
PhyloP100		-0.36
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: rs17765901; hg19: chr8-10249480;