8-10207815-CTTTT-CTTTTTT

Variant names:

• chr8-10207815-C-CTT
• rs77793822
• NM_012331.5:c.143-6_143-5dupTT

Variant summary

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

The NM_012331.5(MSRA):​c.143-6_143-5dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSRA NM_012331.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.143-6_143-5dupTT		splice_region_variant, intron_variant	Intron 1 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.143-6_143-5dupTT		splice_region_variant, intron_variant	Intron 1 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 145002 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00245 AC: 245 AN: 100002 AF XY: 0.00241

Gnomad AFR exome AF: 0.00279

Gnomad AMR exome AF: 0.00283

Gnomad ASJ exome AF: 0.00137

Gnomad EAS exome AF: 0.00371

Gnomad FIN exome AF: 0.00199

Gnomad NFE exome AF: 0.00232

Gnomad OTH exome AF: 0.00201

GnomAD4 exome AF: 0.000770 AC: 884 AN: 1147578 Hom.: 0 Cov.: 0 AF XY: 0.000804 AC XY: 461 AN XY: 573350

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00107 AC: 28 AN: 26072

American (AMR) AF: 0.00152 AC: 52 AN: 34254

Ashkenazi Jewish (ASJ) AF: 0.00113 AC: 24 AN: 21324

East Asian (EAS) AF: 0.000799 AC: 26 AN: 32542

South Asian (SAS) AF: 0.00183 AC: 125 AN: 68146

European-Finnish (FIN) AF: 0.000810 AC: 33 AN: 40730

Middle Eastern (MID) AF: 0.000951 AC: 4 AN: 4208

European-Non Finnish (NFE) AF: 0.000630 AC: 550 AN: 872426

Other (OTH) AF: 0.000877 AC: 42 AN: 47876

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 145002 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 70452

African (AFR) AF: 0.00 AC: 0 AN: 39678

American (AMR) AF: 0.00 AC: 0 AN: 14500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3370

East Asian (EAS) AF: 0.00 AC: 0 AN: 5006

South Asian (SAS) AF: 0.00 AC: 0 AN: 4606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65692

Other (OTH) AF: 0.00 AC: 0 AN: 1976

Alfa AF: 0.00172 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs77793822; hg19: chr8-10065325;