Genetic Variant MSRA:c.143-10_143-5dupTTTTTT (chr8-10207815-C-CTTTTTT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012331.5(MSRA):c.143-10_143-5dupTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000864 in 1,157,124 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.6e-7 ( 0 hom. )

Consequence

MSRA
NM_012331.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.07

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5 link	c.143-10_143-5dupTTTTTT		splice_region_variant, intron_variant	Intron 1 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.143-10_143-5dupTTTTTT		splice_region_variant, intron_variant	Intron 1 of 5	1	NM_012331.5	ENSP00000313921.4		Q9UJ68-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.64e-7

AC:

AN:

1157124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

578220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26286

American (AMR)

AF:

0.00

AC:

AN:

34480

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21482

East Asian (EAS)

AF:

0.00

AC:

AN:

32760

South Asian (SAS)

AF:

0.00

AC:

AN:

68938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4236

European-Non Finnish (NFE)

AF:

0.00000114

AC:

AN:

879698

Other (OTH)

AF:

0.00

AC:

AN:

48266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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8-10207815-CTTTT-CTTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over