1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAA

Variant names:

• chr1-151760903-C-CAAAA
• rs755031728
• NM_031420.4:c.589-8_589-5dupTTTT

Variant summary

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

The NM_031420.4(MRPL9):​c.589-8_589-5dupTTTT 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 0.0068 (23 hom., cov: 0)
  • Exomes 𝑓: 0.015 (34 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 23 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00676 AC: 501 AN: 74114 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00825

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.00632

Gnomad FIN AF: 0.00399

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00459

Gnomad OTH AF: 0.00506

GnomAD4 exome AF: 0.0149 AC: 12918 AN: 867866 Hom.: 34 Cov.: 0 AF XY: 0.0151 AC XY: 6493 AN XY: 431208

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

African (AFR) AF: 0.0208 AC: 363 AN: 17440

American (AMR) AF: 0.0300 AC: 389 AN: 12980

Ashkenazi Jewish (ASJ) AF: 0.0223 AC: 295 AN: 13220

East Asian (EAS) AF: 0.0145 AC: 419 AN: 28870

South Asian (SAS) AF: 0.0172 AC: 741 AN: 43204

European-Finnish (FIN) AF: 0.0156 AC: 373 AN: 23978

Middle Eastern (MID) AF: 0.0216 AC: 57 AN: 2636

European-Non Finnish (NFE) AF: 0.0141 AC: 9680 AN: 688294

Other (OTH) AF: 0.0161 AC: 601 AN: 37244

⚠️ 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: 0.00677 AC: 502 AN: 74108 Hom.: 23 Cov.: 0 AF XY: 0.00728 AC XY: 247 AN XY: 33906

African (AFR) AF: 0.0117 AC: 212 AN: 18058

American (AMR) AF: 0.00825 AC: 54 AN: 6546

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 7 AN: 2206

East Asian (EAS) AF: 0.00910 AC: 24 AN: 2638

South Asian (SAS) AF: 0.00637 AC: 13 AN: 2042

European-Finnish (FIN) AF: 0.00399 AC: 8 AN: 2004

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

European-Non Finnish (NFE) AF: 0.00459 AC: 179 AN: 38970

Other (OTH) AF: 0.00502 AC: 5 AN: 996

Alfa AF: 0.00334 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;