1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAA

Variant names:

• chr1-151760903-C-CA
• rs755031728
• NM_031420.4:c.589-5dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_031420.4(MRPL9):​c.589-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.037 (135 hom., cov: 0)
  • Exomes 𝑓: 0.11 (457 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 2708 AN: 74034 Hom.: 137 Cov.: 0

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.0366

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.0186

Gnomad EAS AF: 0.00831

Gnomad SAS AF: 0.0667

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.0536

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0348

GnomAD4 exome AF: 0.109 AC: 93895 AN: 858534 Hom.: 457 Cov.: 0 AF XY: 0.110 AC XY: 46706 AN XY: 426392

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

African (AFR) AF: 0.116 AC: 2009 AN: 17286

American (AMR) AF: 0.101 AC: 1298 AN: 12860

Ashkenazi Jewish (ASJ) AF: 0.0930 AC: 1221 AN: 13124

East Asian (EAS) AF: 0.0802 AC: 2277 AN: 28388

South Asian (SAS) AF: 0.130 AC: 5540 AN: 42682

European-Finnish (FIN) AF: 0.102 AC: 2428 AN: 23694

Middle Eastern (MID) AF: 0.0979 AC: 255 AN: 2606

European-Non Finnish (NFE) AF: 0.110 AC: 75026 AN: 681088

Other (OTH) AF: 0.104 AC: 3841 AN: 36806

⚠️ 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: 0.0365 AC: 2703 AN: 74028 Hom.: 135 Cov.: 0 AF XY: 0.0360 AC XY: 1219 AN XY: 33894

African (AFR) AF: 0.0341 AC: 615 AN: 18058

American (AMR) AF: 0.0235 AC: 154 AN: 6546

Ashkenazi Jewish (ASJ) AF: 0.0186 AC: 41 AN: 2202

East Asian (EAS) AF: 0.00835 AC: 22 AN: 2636

South Asian (SAS) AF: 0.0652 AC: 133 AN: 2040

European-Finnish (FIN) AF: 0.0249 AC: 50 AN: 2010

Middle Eastern (MID) AF: 0.0588 AC: 6 AN: 102

European-Non Finnish (NFE) AF: 0.0418 AC: 1627 AN: 38902

Other (OTH) AF: 0.0355 AC: 35 AN: 986

Alfa AF: 0.0146 Hom.: 231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs755031728; hg19: chr1-151733379;