chr1-151760903-C-CAAAAAAAAAAAAAAAA

Variant names:

• chr1-151760903-C-CAAAAAAAAAAAAAAAA
• rs755031728
• NM_031420.4:c.589-20_589-5dupTTTTTTTTTTTTTTTT

Variant summary

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

The NM_031420.4(MRPL9):​c.589-20_589-5dupTTTTTTTTTTTTTTTT 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 0.0041 (19 hom., cov: 0)
  • Exomes 𝑓: 0.0029 (13 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 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4	c.589-20_589-5dupTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1
MRPL9	NM_001300733.2	c.487-20_487-5dupTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1
MRPL9	NR_125331.2	n.646-20_646-5dupTTTTTTTTTTTTTTTT		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.589-20_589-5dupTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 302 AN: 74170 Hom.: 19 Cov.: 0

Gnomad AFR AF: 0.00139

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.000765

Gnomad ASJ AF: 0.00452

Gnomad EAS AF: 0.000755

Gnomad SAS AF: 0.000487

Gnomad FIN AF: 0.000998

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00623

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00295 AC: 2581 AN: 876252 Hom.: 13 Cov.: 0 AF XY: 0.00292 AC XY: 1272 AN XY: 435312

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

African (AFR) AF: 0.00135 AC: 24 AN: 17764

American (AMR) AF: 0.00242 AC: 32 AN: 13222

Ashkenazi Jewish (ASJ) AF: 0.00603 AC: 81 AN: 13428

East Asian (EAS) AF: 0.00106 AC: 31 AN: 29318

South Asian (SAS) AF: 0.00138 AC: 60 AN: 43434

European-Finnish (FIN) AF: 0.00397 AC: 96 AN: 24196

Middle Eastern (MID) AF: 0.00263 AC: 7 AN: 2666

European-Non Finnish (NFE) AF: 0.00306 AC: 2123 AN: 694574

Other (OTH) AF: 0.00337 AC: 127 AN: 37650

⚠️ 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: 0.00407 AC: 302 AN: 74164 Hom.: 19 Cov.: 0 AF XY: 0.00389 AC XY: 132 AN XY: 33942

African (AFR) AF: 0.00138 AC: 25 AN: 18076

American (AMR) AF: 0.000765 AC: 5 AN: 6538

Ashkenazi Jewish (ASJ) AF: 0.00452 AC: 10 AN: 2210

East Asian (EAS) AF: 0.000758 AC: 2 AN: 2640

South Asian (SAS) AF: 0.000491 AC: 1 AN: 2038

European-Finnish (FIN) AF: 0.000998 AC: 2 AN: 2004

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

European-Non Finnish (NFE) AF: 0.00623 AC: 243 AN: 39018

Other (OTH) AF: 0.00806 AC: 8 AN: 992

Alfa AF: 0.00322 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

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;