1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAA

Variant names:

• chr1-151760903-C-CAAAAA
• rs755031728
• NM_031420.4:c.589-9_589-5dupTTTTT

Variant summary

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

The NM_031420.4(MRPL9):​c.589-9_589-5dupTTTTT 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 0.00074 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0025 (4 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 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4	c.589-9_589-5dupTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1
MRPL9	NM_001300733.2	c.487-9_487-5dupTTTTT		splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1
MRPL9	NR_125331.2	n.646-9_646-5dupTTTTT		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.589-9_589-5dupTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3

Frequencies

GnomAD3 genomes AF: 0.000755 AC: 56 AN: 74166 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000612

Gnomad ASJ AF: 0.000453

Gnomad EAS AF: 0.000377

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000513

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00254 AC: 2231 AN: 877068 Hom.: 4 Cov.: 0 AF XY: 0.00258 AC XY: 1125 AN XY: 435670

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

African (AFR) AF: 0.00447 AC: 79 AN: 17672

American (AMR) AF: 0.00568 AC: 75 AN: 13194

Ashkenazi Jewish (ASJ) AF: 0.00334 AC: 45 AN: 13486

East Asian (EAS) AF: 0.00273 AC: 80 AN: 29286

South Asian (SAS) AF: 0.00392 AC: 170 AN: 43386

European-Finnish (FIN) AF: 0.00242 AC: 59 AN: 24338

Middle Eastern (MID) AF: 0.00562 AC: 15 AN: 2670

European-Non Finnish (NFE) AF: 0.00229 AC: 1590 AN: 695308

Other (OTH) AF: 0.00313 AC: 118 AN: 37728

⚠️ 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: 0.000742 AC: 55 AN: 74160 Hom.: 2 Cov.: 0 AF XY: 0.000619 AC XY: 21 AN XY: 33950

African (AFR) AF: 0.00161 AC: 29 AN: 18068

American (AMR) AF: 0.000611 AC: 4 AN: 6542

Ashkenazi Jewish (ASJ) AF: 0.000453 AC: 1 AN: 2208

East Asian (EAS) AF: 0.000379 AC: 1 AN: 2640

South Asian (SAS) AF: 0.00 AC: 0 AN: 2044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 100

European-Non Finnish (NFE) AF: 0.000513 AC: 20 AN: 39014

Other (OTH) AF: 0.00 AC: 0 AN: 992

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
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;