1-151760903-CAAAAAAAAAA-CAAAAAAAAAAAAAA

Position:

• chr1-151760903-CAAAAAAAAAA-CAAAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_031420.4(MRPL9):​c.589-5_589-4insTTTT variant causes a splice region, splice polypyrimidine tract, 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 0.0068 (23 hom., cov: 0)
  • Exomes 𝑓: 0.015 (34 hom.)
• Consequence: MRPL9 NM_031420.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0149 (12918/867866) while in subpopulation AMR AF= 0.03 (389/12980). AF 95% confidence interval is 0.0275. There are 34 homozygotes in gnomad4_exome. There are 6493 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00676 AC: 501 AN: 74114 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00825

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.00632

Gnomad FIN AF: 0.00399

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00459

Gnomad OTH AF: 0.00506

GnomAD4 exome AF: 0.0149 AC: 12918 AN: 867866 Hom.: 34 Cov.: 0 AF XY: 0.0151 AC XY: 6493 AN XY: 431208

Gnomad4 AFR exome AF: 0.0208

Gnomad4 AMR exome AF: 0.0300

Gnomad4 ASJ exome AF: 0.0223

Gnomad4 EAS exome AF: 0.0145

Gnomad4 SAS exome AF: 0.0172

Gnomad4 FIN exome AF: 0.0156

Gnomad4 NFE exome AF: 0.0141

Gnomad4 OTH exome AF: 0.0161

GnomAD4 genome AF: 0.00677 AC: 502 AN: 74108 Hom.: 23 Cov.: 0 AF XY: 0.00728 AC XY: 247 AN XY: 33906

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.00825

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00910

Gnomad4 SAS AF: 0.00637

Gnomad4 FIN AF: 0.00399

Gnomad4 NFE AF: 0.00459

Gnomad4 OTH AF: 0.00502

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;