1-151760903-CAAAAA-C

Position:

• chr1-151760903-CAAAAA-C

Variant summary

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

The NM_031420.4(MRPL9):​c.589-9_589-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000894 in 951,064 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: 𝑓 0.000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00096 (0 hom.)
• Consequence: MRPL9 NM_031420.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL9	NM_031420.4	c.589-9_589-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000368830.8
MRPL9	NM_001300733.2	c.487-9_487-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
MRPL9	NR_125331.2	n.646-9_646-5del		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.589-9_589-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_031420.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000674 AC: 5 AN: 74204 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000377

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00893

Gnomad NFE AF: 0.0000768

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000964 AC: 845 AN: 876866 Hom.: 0 AF XY: 0.000976 AC XY: 425 AN XY: 435562

Gnomad4 AFR exome AF: 0.000788

Gnomad4 AMR exome AF: 0.000987

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.000785

Gnomad4 SAS exome AF: 0.00162

Gnomad4 FIN exome AF: 0.000492

Gnomad4 NFE exome AF: 0.000964

Gnomad4 OTH exome AF: 0.000689

GnomAD4 genome AF: 0.0000674 AC: 5 AN: 74198 Hom.: 0 Cov.: 0 AF XY: 0.0000589 AC XY: 2 AN XY: 33964

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000379

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000769

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;