1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAA

Variant names:

• chr1-151760903-C-CAAA
• rs755031728
• NM_031420.4:c.589-7_589-5dupTTT

Variant summary

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

The NM_031420.4(MRPL9):​c.589-7_589-5dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (3078 hom., cov: 0)
  • Exomes 𝑓: 0.074 (249 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 249 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4	c.589-7_589-5dupTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1
MRPL9	NM_001300733.2	c.487-7_487-5dupTTT		splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1
MRPL9	NR_125331.2	n.646-7_646-5dupTTT		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.589-7_589-5dupTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 19234 AN: 73886 Hom.: 3077 Cov.: 0

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.0736 AC: 61867 AN: 840334 Hom.: 249 Cov.: 0 AF XY: 0.0728 AC XY: 30419 AN XY: 417764

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

African (AFR) AF: 0.102 AC: 1706 AN: 16736

American (AMR) AF: 0.112 AC: 1397 AN: 12442

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 1371 AN: 12634

East Asian (EAS) AF: 0.0826 AC: 2238 AN: 27100

South Asian (SAS) AF: 0.0562 AC: 2398 AN: 42662

European-Finnish (FIN) AF: 0.0958 AC: 2193 AN: 22886

Middle Eastern (MID) AF: 0.0996 AC: 251 AN: 2520

European-Non Finnish (NFE) AF: 0.0713 AC: 47573 AN: 667566

Other (OTH) AF: 0.0766 AC: 2740 AN: 35788

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.260 AC: 19237 AN: 73884 Hom.: 3078 Cov.: 0 AF XY: 0.259 AC XY: 8765 AN XY: 33818

African (AFR) AF: 0.247 AC: 4439 AN: 18008

American (AMR) AF: 0.361 AC: 2339 AN: 6482

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 891 AN: 2200

East Asian (EAS) AF: 0.259 AC: 679 AN: 2620

South Asian (SAS) AF: 0.173 AC: 353 AN: 2036

European-Finnish (FIN) AF: 0.203 AC: 407 AN: 2000

Middle Eastern (MID) AF: 0.412 AC: 42 AN: 102

European-Non Finnish (NFE) AF: 0.249 AC: 9688 AN: 38902

Other (OTH) AF: 0.326 AC: 323 AN: 992

Alfa AF: 0.109 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

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

Other links and lift over

dbSNP: rs755031728; hg19: chr1-151733379;