1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr1-151760903-C-CAAAAAAAAAAA
• rs755031728
• NM_031420.4:c.589-15_589-5dupTTTTTTTTTTT

Variant summary

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

The NM_031420.4(MRPL9):​c.589-15_589-5dupTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000081 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: MRPL9 NM_031420.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• 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.589-15_589-5dupTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1
MRPL9	NM_001300733.2	c.487-15_487-5dupTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1
MRPL9	NR_125331.2	n.646-15_646-5dupTTTTTTTTTTT		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.589-15_589-5dupTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3

Frequencies

GnomAD3 genomes AF: 0.0000809 AC: 6 AN: 74202 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000153

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000996

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000768

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000340 AC: 299 AN: 879386 Hom.: 0 Cov.: 0 AF XY: 0.000364 AC XY: 159 AN XY: 436864

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

African (AFR) AF: 0.000281 AC: 5 AN: 17790

American (AMR) AF: 0.000151 AC: 2 AN: 13254

Ashkenazi Jewish (ASJ) AF: 0.000222 AC: 3 AN: 13524

East Asian (EAS) AF: 0.0000340 AC: 1 AN: 29392

South Asian (SAS) AF: 0.000230 AC: 10 AN: 43454

European-Finnish (FIN) AF: 0.000615 AC: 15 AN: 24408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2682

European-Non Finnish (NFE) AF: 0.000363 AC: 253 AN: 697058

Other (OTH) AF: 0.000264 AC: 10 AN: 37824

⚠️ 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: 0.0000809 AC: 6 AN: 74196 Hom.: 1 Cov.: 0 AF XY: 0.0000883 AC XY: 3 AN XY: 33962

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

American (AMR) AF: 0.000153 AC: 1 AN: 6544

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 2638

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

European-Finnish (FIN) AF: 0.000996 AC: 2 AN: 2008

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

European-Non Finnish (NFE) AF: 0.0000769 AC: 3 AN: 39030

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		0.15

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;