chr1-151760903-CAAAAAAAA-C

Variant names:

• chr1-151760903-CAAAAAAAA-C
• rs755031728
• NM_031420.4:c.589-12_589-5delTTTTTTTT

Variant summary

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

The NM_031420.4(MRPL9):​c.589-12_589-5delTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000432 in 879,598 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: not found (cov: 0)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: MRPL9 NM_031420.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• 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 2 ACMG points.

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

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.589-12_589-5delTTTTTTTT		splice_region intron	N/A	NP_113608.1
	MRPL9	NM_001300733.2		c.487-12_487-5delTTTTTTTT		splice_region intron	N/A	NP_001287662.1
	MRPL9	NR_125331.2		n.646-12_646-5delTTTTTTTT		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.589-12_589-5delTTTTTTTT		splice_region intron	N/A	ENSP00000357823.3
	MRPL9	ENST00000368829.3	TSL:2	c.487-12_487-5delTTTTTTTT		splice_region intron	N/A	ENSP00000357822.3
	MRPL9	ENST00000495867.1	TSL:2	n.10_17delTTTTTTTT		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000432 AC: 38 AN: 879598 Hom.: 0 AF XY: 0.0000320 AC XY: 14 AN XY: 436960

⚠️ 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: 13254

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

East Asian (EAS) AF: 0.0000340 AC: 1 AN: 29394

South Asian (SAS) AF: 0.00 AC: 0 AN: 43446

European-Finnish (FIN) AF: 0.0000410 AC: 1 AN: 24418

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

European-Non Finnish (NFE) AF: 0.0000473 AC: 33 AN: 697232

Other (OTH) AF: 0.0000529 AC: 2 AN: 37836

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000555111), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

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;