1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr1-151760903-C-CAAAAAAAA
• rs755031728
• NM_031420.4:c.589-12_589-5dupTTTTTTTT

Variant summary

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

The NM_031420.4(MRPL9):​c.589-12_589-5dupTTTTTTTT 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 0.0024 (4 hom., cov: 0)
  • Exomes 𝑓: 0.00016 (1 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 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4	c.589-12_589-5dupTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1
MRPL9	NM_001300733.2	c.487-12_487-5dupTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1
MRPL9	NR_125331.2	n.646-12_646-5dupTTTTTTTT		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.589-12_589-5dupTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 178 AN: 74158 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00944

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000256

Gnomad OTH AF: 0.00304

GnomAD4 exome AF: 0.000163 AC: 143 AN: 879584 Hom.: 1 Cov.: 0 AF XY: 0.000197 AC XY: 86 AN XY: 436970

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

African (AFR) AF: 0.00175 AC: 31 AN: 17764

American (AMR) AF: 0.000302 AC: 4 AN: 13256

Ashkenazi Jewish (ASJ) AF: 0.000222 AC: 3 AN: 13542

East Asian (EAS) AF: 0.00 AC: 0 AN: 29398

South Asian (SAS) AF: 0.000368 AC: 16 AN: 43464

European-Finnish (FIN) AF: 0.0000410 AC: 1 AN: 24414

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

European-Non Finnish (NFE) AF: 0.000119 AC: 83 AN: 697226

Other (OTH) AF: 0.000132 AC: 5 AN: 37836

⚠️ 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: 0.00240 AC: 178 AN: 74152 Hom.: 4 Cov.: 0 AF XY: 0.00253 AC XY: 86 AN XY: 33946

African (AFR) AF: 0.00942 AC: 170 AN: 18040

American (AMR) AF: 0.000459 AC: 3 AN: 6540

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: 2044

European-Finnish (FIN) AF: 0.000499 AC: 1 AN: 2004

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

European-Non Finnish (NFE) AF: 0.0000256 AC: 1 AN: 39030

Other (OTH) AF: 0.00302 AC: 3 AN: 994

Alfa AF: 0.00 Hom.: 231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;