chr8-10129145-G-C

Variant names:

• chr8-10129145-G-C
• rs1484642
• NM_012331.5:c.142+74487G>C

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+74487G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 152,216 control chromosomes in the GnomAD database, including 63,207 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 0.91 (63207 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• 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]

ENSG00000285675 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 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.142+74487G>C		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.142+74487G>C		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.13+33102G>C		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.142+74487G>C		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.13+33102G>C		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.-57+32827G>C		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138466 AN: 152098 Hom.: 63158 Cov.: 31

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.910 AC: 138574 AN: 152216 Hom.: 63207 Cov.: 31 AF XY: 0.910 AC XY: 67691 AN XY: 74398

African (AFR) AF: 0.856 AC: 35570 AN: 41538

American (AMR) AF: 0.947 AC: 14486 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 3334 AN: 3472

East Asian (EAS) AF: 0.965 AC: 4969 AN: 5150

South Asian (SAS) AF: 0.896 AC: 4320 AN: 4822

European-Finnish (FIN) AF: 0.910 AC: 9643 AN: 10600

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63122 AN: 68028

Other (OTH) AF: 0.930 AC: 1965 AN: 2112

Alfa AF: 0.925 Hom.: 36102

Bravo AF: 0.914

Asia WGS AF: 0.913 AC: 3175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		-0.23
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: rs1484642; hg19: chr8-9986655;