1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr1-151760903-C-CAAAAAAAAAAAAAAA
• rs755031728
• NM_031420.4:c.589-19_589-5dupTTTTTTTTTTTTTTT

Variant summary

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

The NM_031420.4(MRPL9):​c.589-19_589-5dupTTTTTTTTTTTTTTT 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 0.023 (157 hom., cov: 0)
  • Exomes 𝑓: 0.0036 (14 hom.)
  • Failed GnomAD Quality Control
• 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 GnomAdExome4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031420.4. 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.589-19_589-5dupTTTTTTTTTTTTTTT		splice_region intron	N/A	NP_113608.1
	MRPL9	NM_001300733.2		c.487-19_487-5dupTTTTTTTTTTTTTTT		splice_region intron	N/A	NP_001287662.1
	MRPL9	NR_125331.2		n.646-19_646-5dupTTTTTTTTTTTTTTT		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.589-19_589-5dupTTTTTTTTTTTTTTT		splice_region intron	N/A	ENSP00000357823.3
	MRPL9	ENST00000368829.3	TSL:2	c.487-19_487-5dupTTTTTTTTTTTTTTT		splice_region intron	N/A	ENSP00000357822.3
	MRPL9	ENST00000495867.1	TSL:2	n.3_17dupTTTTTTTTTTTTTTT		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 1679 AN: 74112 Hom.: 157 Cov.: 0

Gnomad AFR AF: 0.00582

Gnomad AMI AF: 0.0311

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.00227

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.00399

Gnomad MID AF: 0.00893

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.0255

GnomAD4 exome AF: 0.00362 AC: 3166 AN: 875472 Hom.: 14 Cov.: 0 AF XY: 0.00368 AC XY: 1601 AN XY: 434876

⚠️ 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: 17766

American (AMR) AF: 0.00227 AC: 30 AN: 13210

Ashkenazi Jewish (ASJ) AF: 0.00566 AC: 76 AN: 13434

East Asian (EAS) AF: 0.00143 AC: 42 AN: 29298

South Asian (SAS) AF: 0.00154 AC: 67 AN: 43428

European-Finnish (FIN) AF: 0.00463 AC: 112 AN: 24178

Middle Eastern (MID) AF: 0.00411 AC: 11 AN: 2674

European-Non Finnish (NFE) AF: 0.00384 AC: 2665 AN: 693918

Other (OTH) AF: 0.00370 AC: 139 AN: 37566

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0227 AC: 1679 AN: 74106 Hom.: 157 Cov.: 0 AF XY: 0.0205 AC XY: 694 AN XY: 33918

African (AFR) AF: 0.00581 AC: 105 AN: 18076

American (AMR) AF: 0.0104 AC: 68 AN: 6532

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 73 AN: 2206

East Asian (EAS) AF: 0.00228 AC: 6 AN: 2636

South Asian (SAS) AF: 0.0127 AC: 26 AN: 2044

European-Finnish (FIN) AF: 0.00399 AC: 8 AN: 2006

Middle Eastern (MID) AF: 0.00980 AC: 1 AN: 102

European-Non Finnish (NFE) AF: 0.0346 AC: 1350 AN: 38968

Other (OTH) AF: 0.0253 AC: 25 AN: 990

Alfa AF: 0.0106 Hom.: 231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;