1-151760891-A-G

Variant names:

• chr1-151760891-A-G
• rs1471493126
• NM_031420.4:c.597T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_031420.4(MRPL9):​c.597T>C​(p.Val199Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V199V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MRPL9 NM_031420.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.408 with no splicing effect.

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.597T>C	p.Val199Val	synonymous	Exon 6 of 7	NP_113608.1	Q9BYD2
	MRPL9	NM_001300733.2		c.495T>C	p.Val165Val	synonymous	Exon 5 of 6	NP_001287662.1	Q5SZR1
	MRPL9	NR_125331.2		n.654T>C		non_coding_transcript_exon	Exon 6 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL9	ENST00000368830.8	TSL:1 MANE Select	c.597T>C	p.Val199Val	synonymous	Exon 6 of 7	ENSP00000357823.3	Q9BYD2
	MRPL9	ENST00000368829.3	TSL:2	c.495T>C	p.Val165Val	synonymous	Exon 5 of 6	ENSP00000357822.3	Q5SZR1
	MRPL9	ENST00000467306.5	TSL:2	n.*268T>C		non_coding_transcript_exon	Exon 6 of 7	ENSP00000492374.1	A0A1W2PRK9

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381282 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 688236

African (AFR) AF: 0.00 AC: 0 AN: 29216

American (AMR) AF: 0.00 AC: 0 AN: 30202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23192

East Asian (EAS) AF: 0.00 AC: 0 AN: 38412

South Asian (SAS) AF: 0.00 AC: 0 AN: 76382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5420

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077534

Other (OTH) AF: 0.00 AC: 0 AN: 56732

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.6
DANN	Benign	0.61
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs1471493126; hg19: chr1-151733367;