1-151760903-CAAAAAAAAAAAA-CAAAAA

Variant names:

• chr1-151760903-CAAAAAAA-C
• rs755031728
• NM_031420.4:c.589-11_589-5delTTTTTTT

Variant summary

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

The NM_031420.4(MRPL9):​c.589-11_589-5delTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 953,520 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: 0.00012 (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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031420.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL9	NM_031420.4	MANE Select	c.589-11_589-5delTTTTTTT		splice_region intron	N/A	NP_113608.1
	MRPL9	NM_001300733.2		c.487-11_487-5delTTTTTTT		splice_region intron	N/A	NP_001287662.1
	MRPL9	NR_125331.2		n.646-11_646-5delTTTTTTT		splice_region intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL9	ENST00000368830.8	TSL:1 MANE Select	c.589-11_589-5delTTTTTTT		splice_region intron	N/A	ENSP00000357823.3
	MRPL9	ENST00000495867.1	TSL:2	n.11_17delTTTTTTT		non_coding_transcript_exon	Exon 1 of 2
	MRPL9	ENST00000368829.3	TSL:2	c.487-11_487-5delTTTTTTT		splice_region intron	N/A	ENSP00000357822.3

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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000128

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000121 AC: 106 AN: 879316 Hom.: 0 AF XY: 0.000121 AC XY: 53 AN XY: 436804

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

African (AFR) AF: 0.0000562 AC: 1 AN: 17790

American (AMR) AF: 0.000227 AC: 3 AN: 13238

Ashkenazi Jewish (ASJ) AF: 0.0000739 AC: 1 AN: 13536

East Asian (EAS) AF: 0.00 AC: 0 AN: 29392

South Asian (SAS) AF: 0.000253 AC: 11 AN: 43404

European-Finnish (FIN) AF: 0.0000819 AC: 2 AN: 24408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2684

European-Non Finnish (NFE) AF: 0.000118 AC: 82 AN: 697040

Other (OTH) AF: 0.000159 AC: 6 AN: 37824

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000674 AC: 5 AN: 74204 Hom.: 0 Cov.: 0 AF XY: 0.0000589 AC XY: 2 AN XY: 33958

African (AFR) AF: 0.00 AC: 0 AN: 18052

American (AMR) AF: 0.00 AC: 0 AN: 6542

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 2650

South Asian (SAS) AF: 0.00 AC: 0 AN: 2058

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 112

European-Non Finnish (NFE) AF: 0.000128 AC: 5 AN: 39040

Other (OTH) AF: 0.00 AC: 0 AN: 986

Alfa AF: 0.00 Hom.: 231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
Mutation Taster		=94/6	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;