1-151760903-CAAAAAAAAAAAA-CAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031420.4(MRPL9):​c.589-7_589-5delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00922 in 939,378 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.010 (0 hom.)
• Consequence: MRPL9 NM_031420.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Variant has high frequency in the SAS (0.0151) population. However there is too low homozygotes in high coverage region: (expected more than 19, got 0).

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.589-7_589-5delTTT		splice_region intron	N/A	NP_113608.1
	MRPL9	NM_001300733.2		c.487-7_487-5delTTT		splice_region intron	N/A	NP_001287662.1
	MRPL9	NR_125331.2		n.646-7_646-5delTTT		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.589-7_589-5delTTT		splice_region intron	N/A	ENSP00000357823.3
	MRPL9	ENST00000495867.1	TSL:2	n.15_17delTTT		non_coding_transcript_exon	Exon 1 of 2
	MRPL9	ENST00000368829.3	TSL:2	c.487-7_487-5delTTT		splice_region intron	N/A	ENSP00000357822.3

Frequencies

GnomAD3 genomes AF: 0.000162 AC: 12 AN: 74196 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000153

Gnomad ASJ AF: 0.00136

Gnomad EAS AF: 0.000377

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000512

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0100 AC: 8651 AN: 865188 Hom.: 0 AF XY: 0.0102 AC XY: 4364 AN XY: 429496

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

African (AFR) AF: 0.00763 AC: 134 AN: 17566

American (AMR) AF: 0.0118 AC: 153 AN: 12978

Ashkenazi Jewish (ASJ) AF: 0.00722 AC: 96 AN: 13288

East Asian (EAS) AF: 0.00761 AC: 219 AN: 28782

South Asian (SAS) AF: 0.0161 AC: 684 AN: 42420

European-Finnish (FIN) AF: 0.00717 AC: 172 AN: 23990

Middle Eastern (MID) AF: 0.00946 AC: 25 AN: 2642

European-Non Finnish (NFE) AF: 0.00989 AC: 6789 AN: 686280

Other (OTH) AF: 0.0102 AC: 379 AN: 37242

⚠️ 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: 0.000162 AC: 12 AN: 74190 Hom.: 0 Cov.: 0 AF XY: 0.000206 AC XY: 7 AN XY: 33958

African (AFR) AF: 0.000221 AC: 4 AN: 18078

American (AMR) AF: 0.000153 AC: 1 AN: 6546

Ashkenazi Jewish (ASJ) AF: 0.00136 AC: 3 AN: 2212

East Asian (EAS) AF: 0.000379 AC: 1 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: 0.0000513 AC: 2 AN: 39024

Other (OTH) AF: 0.00 AC: 0 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		1.9
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs755031728; hg19: chr1-151733379;