1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr1-151760903-C-CAAAAAAAAAAAAAAAAA
• rs755031728
• NM_031420.4:c.589-21_589-5dupTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_031420.4(MRPL9):​c.589-21_589-5dupTTTTTTTTTTTTTTTTT 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 0.0019 (11 hom., cov: 0)
  • Exomes 𝑓: 0.0017 (4 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4	c.589-21_589-5dupTTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1
MRPL9	NM_001300733.2	c.487-21_487-5dupTTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1
MRPL9	NR_125331.2	n.646-21_646-5dupTTTTTTTTTTTTTTTTT		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.589-21_589-5dupTTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 143 AN: 74184 Hom.: 11 Cov.: 0

Gnomad AFR AF: 0.000665

Gnomad AMI AF: 0.00366

Gnomad AMR AF: 0.00122

Gnomad ASJ AF: 0.00452

Gnomad EAS AF: 0.000378

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.000499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00267

Gnomad OTH AF: 0.00203

GnomAD4 exome AF: 0.00167 AC: 1465 AN: 877674 Hom.: 4 Cov.: 0 AF XY: 0.00174 AC XY: 757 AN XY: 435996

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

African (AFR) AF: 0.000507 AC: 9 AN: 17768

American (AMR) AF: 0.00143 AC: 19 AN: 13242

Ashkenazi Jewish (ASJ) AF: 0.00252 AC: 34 AN: 13488

East Asian (EAS) AF: 0.000715 AC: 21 AN: 29360

South Asian (SAS) AF: 0.000852 AC: 37 AN: 43436

European-Finnish (FIN) AF: 0.00239 AC: 58 AN: 24278

Middle Eastern (MID) AF: 0.00299 AC: 8 AN: 2674

European-Non Finnish (NFE) AF: 0.00173 AC: 1206 AN: 695686

Other (OTH) AF: 0.00193 AC: 73 AN: 37742

⚠️ 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: 0.00193 AC: 143 AN: 74178 Hom.: 11 Cov.: 0 AF XY: 0.00150 AC XY: 51 AN XY: 33956

African (AFR) AF: 0.000664 AC: 12 AN: 18076

American (AMR) AF: 0.00122 AC: 8 AN: 6544

Ashkenazi Jewish (ASJ) AF: 0.00452 AC: 10 AN: 2212

East Asian (EAS) AF: 0.000379 AC: 1 AN: 2638

South Asian (SAS) AF: 0.00147 AC: 3 AN: 2044

European-Finnish (FIN) AF: 0.000499 AC: 1 AN: 2006

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

European-Non Finnish (NFE) AF: 0.00267 AC: 104 AN: 39016

Other (OTH) AF: 0.00201 AC: 2 AN: 994

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=100/0	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;