NM_012331.5:c.142+21067G>A

Variant names:

• chr8-10075725-G-A
• rs3735823
• NM_012331.5:c.142+21067G>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.142+21067G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,064 control chromosomes in the GnomAD database, including 22,955 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 0.52 (22955 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.897
• 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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	NM_012331.5	MANE Select	c.142+21067G>A		intron	N/A	NP_036463.1	Q9UJ68-1
	MSRA	NM_001135670.3		c.142+21067G>A		intron	N/A	NP_001129142.1	Q9UJ68-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	ENST00000317173.9	TSL:1 MANE Select	c.142+21067G>A		intron	N/A	ENSP00000313921.4	Q9UJ68-1
	MSRA	ENST00000897533.1		c.142+21067G>A		intron	N/A	ENSP00000567592.1
	MSRA	ENST00000897536.1		c.142+21067G>A		intron	N/A	ENSP00000567595.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79580 AN: 151946 Hom.: 22970 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.523 AC: 79550 AN: 152064 Hom.: 22955 Cov.: 33 AF XY: 0.525 AC XY: 38998 AN XY: 74340

African (AFR) AF: 0.264 AC: 10960 AN: 41462

American (AMR) AF: 0.560 AC: 8555 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2432 AN: 3468

East Asian (EAS) AF: 0.532 AC: 2746 AN: 5164

South Asian (SAS) AF: 0.490 AC: 2358 AN: 4816

European-Finnish (FIN) AF: 0.648 AC: 6853 AN: 10580

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43525 AN: 67972

Other (OTH) AF: 0.569 AC: 1202 AN: 2114

Alfa AF: 0.567 Hom.: 5518

Bravo AF: 0.508

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.7
DANN	Benign	0.52
PhyloP100		0.90
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: rs3735823; hg19: chr8-9933235;