1-151760903-CAAAAAAAAAAAA-CAAA

Variant names:

• chr1-151760903-CAAAAAAAAA-C
• rs755031728
• NM_031420.4:c.589-13_589-5delTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031420.4(MRPL9):​c.589-13_589-5delTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 953,866 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 0.000013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: MRPL9 NM_031420.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16
• Publications: 0 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4	c.589-13_589-5delTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1
MRPL9	NM_001300733.2	c.487-13_487-5delTTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1
MRPL9	NR_125331.2	n.646-13_646-5delTTTTTTTTT		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.589-13_589-5delTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 1 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: 0.00

Gnomad SAS AF: 0.000486

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000148 AC: 13 AN: 879668 Hom.: 0 AF XY: 0.0000137 AC XY: 6 AN XY: 437010

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

African (AFR) AF: 0.00 AC: 0 AN: 17792

American (AMR) AF: 0.0000754 AC: 1 AN: 13256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13542

East Asian (EAS) AF: 0.00 AC: 0 AN: 29398

South Asian (SAS) AF: 0.0000460 AC: 2 AN: 43452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24416

Middle Eastern (MID) AF: 0.000373 AC: 1 AN: 2684

European-Non Finnish (NFE) AF: 0.0000115 AC: 8 AN: 697286

Other (OTH) AF: 0.0000264 AC: 1 AN: 37842

⚠️ 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: 0.0000135 AC: 1 AN: 74198 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 2640

South Asian (SAS) AF: 0.000489 AC: 1 AN: 2044

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 102

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 39032

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

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;