8-10207815-CTT-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_012331.5(MSRA):c.143-6_143-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000959 in 1,280,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: MSRA NM_012331.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.07

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-10207815-CTT-C is Benign according to our data. Variant chr8-10207815-CTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3038398.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRA	NM_012331.5	c.143-6_143-5del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000317173.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9	c.143-6_143-5del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_012331.5	P1

Frequencies

GnomAD3 genomes AF: 0.0000276 AC: 4 AN: 144984 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000504

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: 0.000223

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00108 AC: 1224 AN: 1135894 Hom.: 0 AF XY: 0.00112 AC XY: 638 AN XY: 567274

Gnomad4 AFR exome AF: 0.00174

Gnomad4 AMR exome AF: 0.00313

Gnomad4 ASJ exome AF: 0.00162

Gnomad4 EAS exome AF: 0.000968

Gnomad4 SAS exome AF: 0.00228

Gnomad4 FIN exome AF: 0.00222

Gnomad4 NFE exome AF: 0.000806

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.0000276 AC: 4 AN: 144984 Hom.: 0 Cov.: 32 AF XY: 0.0000284 AC XY: 2 AN XY: 70448

Gnomad4 AFR AF: 0.0000504

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000223

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MSRA-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 22, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs77793822; hg19: chr8-10065325;