1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAAA

Variant names:

• chr1-151760903-C-CAA
• rs755031728
• NM_031420.4:c.589-6_589-5dupTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_031420.4(MRPL9):​c.589-6_589-5dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (1889 hom., cov: 0)
  • Exomes 𝑓: 0.099 (482 hom.)
• Consequence: MRPL9 NM_031420.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-151760903-C-CAA is Benign according to our data. Variant chr1-151760903-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 403108.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL9	NM_031420.4	MANE Select	c.589-6_589-5dupTT		splice_region intron	N/A	NP_113608.1	Q9BYD2
	MRPL9	NM_001300733.2		c.487-6_487-5dupTT		splice_region intron	N/A	NP_001287662.1	Q5SZR1
	MRPL9	NR_125331.2		n.646-6_646-5dupTT		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL9	ENST00000368830.8	TSL:1 MANE Select	c.589-6_589-5dupTT		splice_region intron	N/A	ENSP00000357823.3	Q9BYD2
	MRPL9	ENST00000368829.3	TSL:2	c.487-6_487-5dupTT		splice_region intron	N/A	ENSP00000357822.3	Q5SZR1
	MRPL9	ENST00000495867.1	TSL:2	n.16_17dupTT		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.189 AC: 14017 AN: 74010 Hom.: 1891 Cov.: 0

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0982

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.0994 AC: 83209 AN: 836750 Hom.: 482 Cov.: 0 AF XY: 0.0987 AC XY: 41054 AN XY: 415996

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

African (AFR) AF: 0.145 AC: 2421 AN: 16664

American (AMR) AF: 0.113 AC: 1416 AN: 12586

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 1359 AN: 12688

East Asian (EAS) AF: 0.0806 AC: 2197 AN: 27260

South Asian (SAS) AF: 0.0848 AC: 3596 AN: 42406

European-Finnish (FIN) AF: 0.120 AC: 2742 AN: 22892

Middle Eastern (MID) AF: 0.0960 AC: 243 AN: 2532

European-Non Finnish (NFE) AF: 0.0988 AC: 65562 AN: 663912

Other (OTH) AF: 0.103 AC: 3673 AN: 35810

⚠️ 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: 0.189 AC: 14013 AN: 74002 Hom.: 1889 Cov.: 0 AF XY: 0.187 AC XY: 6324 AN XY: 33870

African (AFR) AF: 0.268 AC: 4825 AN: 18004

American (AMR) AF: 0.152 AC: 990 AN: 6534

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 278 AN: 2212

East Asian (EAS) AF: 0.133 AC: 349 AN: 2628

South Asian (SAS) AF: 0.122 AC: 249 AN: 2038

European-Finnish (FIN) AF: 0.160 AC: 320 AN: 1996

Middle Eastern (MID) AF: 0.0882 AC: 9 AN: 102

European-Non Finnish (NFE) AF: 0.172 AC: 6685 AN: 38956

Other (OTH) AF: 0.159 AC: 157 AN: 990

Alfa AF: 0.0572 Hom.: 231

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs755031728;

hg19: chr1-151733379;