NM_031420.4:c.589-17_589-5dupTTTTTTTTTTTTT

Variant names:

• chr1-151760903-C-CAAAAAAAAAAAAA
• rs755031728
• NM_031420.4:c.589-17_589-5dupTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_031420.4(MRPL9):​c.589-17_589-5dupTTTTTTTTTTTTT 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0015 (13 hom.)
• Consequence: MRPL9 NM_031420.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -6 ACMG points.

• BP6: Variant 1-151760903-C-CAAAAAAAAAAAAA is Benign according to our data. Variant chr1-151760903-C-CAAAAAAAAAAAAA is described in ClinVar as [Likely_benign]. Clinvar id is 3770390.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4	c.589-17_589-5dupTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1
MRPL9	NM_001300733.2	c.487-17_487-5dupTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1
MRPL9	NR_125331.2	n.646-17_646-5dupTTTTTTTTTTTTT		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.589-17_589-5dupTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 8 AN: 74202 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000554

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000154

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00149 AC: 1304 AN: 877932 Hom.: 13 Cov.: 0 AF XY: 0.00150 AC XY: 652 AN XY: 436052

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

African (AFR) AF: 0.000450 AC: 8 AN: 17768

American (AMR) AF: 0.000679 AC: 9 AN: 13246

Ashkenazi Jewish (ASJ) AF: 0.00223 AC: 30 AN: 13468

East Asian (EAS) AF: 0.000511 AC: 15 AN: 29362

South Asian (SAS) AF: 0.000967 AC: 42 AN: 43454

European-Finnish (FIN) AF: 0.00152 AC: 37 AN: 24304

Middle Eastern (MID) AF: 0.000748 AC: 2 AN: 2674

European-Non Finnish (NFE) AF: 0.00158 AC: 1101 AN: 695894

Other (OTH) AF: 0.00159 AC: 60 AN: 37762

⚠️ 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: 0.000108 AC: 8 AN: 74202 Hom.: 0 Cov.: 0 AF XY: 0.000118 AC XY: 4 AN XY: 33958

African (AFR) AF: 0.0000554 AC: 1 AN: 18050

American (AMR) AF: 0.000153 AC: 1 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: 0.000154 AC: 6 AN: 39040

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

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MRPL9: BP4, BS2 -

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;