1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAA

Variant names:

• chr1-151760903-CA-C
• rs755031728
• NM_031420.4:c.589-5delT

Variant summary

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

The NM_031420.4(MRPL9):​c.589-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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 0.0022 (1 hom., cov: 0)
  • Exomes 𝑓: 0.14 (0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00220 AC: 163 AN: 74198 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00532

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000377

Gnomad SAS AF: 0.00583

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000410

Gnomad OTH AF: 0.00203

GnomAD4 exome AF: 0.143 AC: 121890 AN: 852606 Hom.: 0 Cov.: 0 AF XY: 0.143 AC XY: 60367 AN XY: 423162

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

African (AFR) AF: 0.0920 AC: 1594 AN: 17324

American (AMR) AF: 0.115 AC: 1466 AN: 12734

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 1520 AN: 13124

East Asian (EAS) AF: 0.152 AC: 4231 AN: 27912

South Asian (SAS) AF: 0.149 AC: 6169 AN: 41456

European-Finnish (FIN) AF: 0.126 AC: 2935 AN: 23334

Middle Eastern (MID) AF: 0.123 AC: 319 AN: 2602

European-Non Finnish (NFE) AF: 0.146 AC: 98623 AN: 677560

Other (OTH) AF: 0.138 AC: 5033 AN: 36560

⚠️ 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: 0.00221 AC: 164 AN: 74192 Hom.: 1 Cov.: 0 AF XY: 0.00224 AC XY: 76 AN XY: 33962

African (AFR) AF: 0.00537 AC: 97 AN: 18076

American (AMR) AF: 0.00199 AC: 13 AN: 6544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2212

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

South Asian (SAS) AF: 0.00587 AC: 12 AN: 2044

European-Finnish (FIN) AF: 0.0115 AC: 23 AN: 2006

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

European-Non Finnish (NFE) AF: 0.000410 AC: 16 AN: 39028

Other (OTH) AF: 0.00201 AC: 2 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
Mutation Taster		=100/0	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;