1-151760903-CAAAAAAAAAAAA-CAAAAAAA

Variant names:

• chr1-151760903-CAAAAA-C
• rs755031728
• NM_031420.4:c.589-9_589-5delTTTTT

Variant summary

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

The NM_031420.4(MRPL9):​c.589-9_589-5delTTTTT variant causes a splice region, 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, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4	c.589-9_589-5delTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1
MRPL9	NM_001300733.2	c.487-9_487-5delTTTTT		splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1
MRPL9	NR_125331.2	n.646-9_646-5delTTTTT		splice_region_variant, intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL9	ENST00000368830.8	c.589-9_589-5delTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3

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

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

African (AFR) AF: 0.000788 AC: 14 AN: 17756

American (AMR) AF: 0.000987 AC: 13 AN: 13174

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 15 AN: 13502

East Asian (EAS) AF: 0.000785 AC: 23 AN: 29292

South Asian (SAS) AF: 0.00162 AC: 70 AN: 43194

European-Finnish (FIN) AF: 0.000492 AC: 12 AN: 24370

Middle Eastern (MID) AF: 0.000747 AC: 2 AN: 2678

European-Non Finnish (NFE) AF: 0.000964 AC: 670 AN: 695164

Other (OTH) AF: 0.000689 AC: 26 AN: 37736

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

African (AFR) AF: 0.00 AC: 0 AN: 18078

American (AMR) AF: 0.00 AC: 0 AN: 6544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2212

East Asian (EAS) AF: 0.000379 AC: 1 AN: 2640

South Asian (SAS) AF: 0.00 AC: 0 AN: 2044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2006

Middle Eastern (MID) AF: 0.00980 AC: 1 AN: 102

European-Non Finnish (NFE) AF: 0.0000769 AC: 3 AN: 39032

Other (OTH) AF: 0.00 AC: 0 AN: 994

Alfa AF: 0.00 Hom.: 231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
Mutation Taster		=93/7	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs755031728; hg19: chr1-151733379;