chr1-151760903-C-CAA

Position:

• chr1-151760903-C-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_031420.4(MRPL9):​c.589-5_589-4insTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (1889 hom., cov: 0)
  • Exomes 𝑓: 0.099 (482 hom.)
• Consequence: MRPL9 NM_031420.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.153

Genes affected

MRPL9 (HGNC:14277): (mitochondrial ribosomal protein L9) This is a nuclear gene encoding a protein component of the 39S subunit of the mitochondrial ribosome. Alternative splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 8. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-151760903-C-CAA is Benign according to our data. Variant chr1-151760903-C-CAA is described in ClinVar as [Benign]. Clinvar id is 403108.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL9	NM_031420.4	c.589-5_589-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000368830.8
MRPL9	NM_001300733.2	c.487-5_487-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
MRPL9	NR_125331.2	n.646-5_646-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL9	ENST00000368830.8	c.589-5_589-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_031420.4	P1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 14017 AN: 74010 Hom.: 1891 Cov.: 0

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0982

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.0994 AC: 83209 AN: 836750 Hom.: 482 Cov.: 0 AF XY: 0.0987 AC XY: 41054 AN XY: 415996

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.0806

Gnomad4 SAS exome AF: 0.0848

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.0988

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.189 AC: 14013 AN: 74002 Hom.: 1889 Cov.: 0 AF XY: 0.187 AC XY: 6324 AN XY: 33870

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.159

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs755031728; hg19: chr1-151733379;