1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr1-151760903-C-CAAAAAAAAAAAAAAAAAA
• rs755031728
• NM_031420.4:c.589-22_589-5dupTTTTTTTTTTTTTTTTTT

Variant summary

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

The ENST00000368830.8(MRPL9):​c.589-5_589-4insTTTTTTTTTTTTTTTTTT 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 0.0012 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00081 (5 hom.)
• Consequence: MRPL9 ENST00000368830.8 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 GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368830.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL9	NM_031420.4	MANE Select	c.589-22_589-5dupTTTTTTTTTTTTTTTTTT		splice_region intron	N/A	NP_113608.1
	MRPL9	NM_001300733.2		c.487-22_487-5dupTTTTTTTTTTTTTTTTTT		splice_region intron	N/A	NP_001287662.1
	MRPL9	NR_125331.2		n.646-22_646-5dupTTTTTTTTTTTTTTTTTT		splice_region intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL9	ENST00000368830.8	TSL:1 MANE Select	c.589-5_589-4insTTTTTTTTTTTTTTTTTT		splice_region intron	N/A	ENSP00000357823.3
	MRPL9	ENST00000495867.1	TSL:2	n.17_18insTTTTTTTTTTTTTTTTTT		non_coding_transcript_exon	Exon 1 of 2
	MRPL9	ENST00000368829.3	TSL:2	c.487-5_487-4insTTTTTTTTTTTTTTTTTT		splice_region intron	N/A	ENSP00000357822.3

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 88 AN: 74188 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00366

Gnomad AMR AF: 0.000764

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000997

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.00101

GnomAD4 exome AF: 0.000812 AC: 714 AN: 878800 Hom.: 5 Cov.: 0 AF XY: 0.000859 AC XY: 375 AN XY: 436542

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

African (AFR) AF: 0.000506 AC: 9 AN: 17774

American (AMR) AF: 0.000378 AC: 5 AN: 13234

Ashkenazi Jewish (ASJ) AF: 0.00104 AC: 14 AN: 13502

East Asian (EAS) AF: 0.000306 AC: 9 AN: 29378

South Asian (SAS) AF: 0.000483 AC: 21 AN: 43448

European-Finnish (FIN) AF: 0.00107 AC: 26 AN: 24358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2684

European-Non Finnish (NFE) AF: 0.000844 AC: 588 AN: 696636

Other (OTH) AF: 0.00111 AC: 42 AN: 37786

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00119 AC: 88 AN: 74182 Hom.: 1 Cov.: 0 AF XY: 0.000972 AC XY: 33 AN XY: 33954

African (AFR) AF: 0.00166 AC: 30 AN: 18078

American (AMR) AF: 0.000764 AC: 5 AN: 6544

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 2640

South Asian (SAS) AF: 0.00 AC: 0 AN: 2042

European-Finnish (FIN) AF: 0.000997 AC: 2 AN: 2006

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

European-Non Finnish (NFE) AF: 0.00123 AC: 48 AN: 39018

Other (OTH) AF: 0.00101 AC: 1 AN: 994

Alfa AF: 0.00 Hom.: 231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;