Genetic Variant MSRA:c.543+23425G>T (chr8-10343414-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_012331.5(MSRA):c.543+23425G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,210 control chromosomes in the GnomAD database, including 54,413 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 0.84 ( 54413 hom., cov: 33)

Consequence

MSRA
NM_012331.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.653

Variant links:

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]

MSRA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5 link	c.543+23425G>T		intron_variant	Intron 5 of 5	ENST00000317173.9	NP_036463.1	Q9UJ68-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9 link	c.543+23425G>T		intron_variant	Intron 5 of 5	1	NM_012331.5	ENSP00000313921.4		Q9UJ68-1

Frequencies

GnomAD3 genomes

AF:

0.840

AC:

127812

AN:

152092

Hom.:

54378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.702

Gnomad AMI

AF:

0.881

Gnomad AMR

AF:

0.889

Gnomad ASJ

AF:

0.909

Gnomad EAS

AF:

0.682

Gnomad SAS

AF:

0.933

Gnomad FIN

AF:

0.904

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.904

Gnomad OTH

AF:

0.867

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

GnomAD4 genome

AF:

0.840

AC:

127899

AN:

152210

Hom.:

54413

Cov.:

AF XY:

0.841

AC XY:

62559

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.702

Gnomad4 AMR

AF:

0.889

Gnomad4 ASJ

AF:

0.909

Gnomad4 EAS

AF:

0.682

Gnomad4 SAS

AF:

0.933

Gnomad4 FIN

AF:

0.904

Gnomad4 NFE

AF:

0.904

Gnomad4 OTH

AF:

0.868

Alfa

AF:

0.870

Hom.:

12815

Bravo

AF:

0.832

Asia WGS

AF:

0.817

AC:

2840

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over