rs1471493126

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-151760891-A-C
• chr1-151760891-A-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_031420.4(MRPL9):​c.597T>G​(p.Val199Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000393 in 1,527,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: MRPL9 NM_031420.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 1-151760891-A-C is Benign according to our data. Variant chr1-151760891-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2639181.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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>G	p.Val199Val	synonymous	Exon 6 of 7	NP_113608.1	Q9BYD2
	MRPL9	NM_001300733.2		c.495T>G	p.Val165Val	synonymous	Exon 5 of 6	NP_001287662.1	Q5SZR1
	MRPL9	NR_125331.2		n.654T>G		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>G	p.Val199Val	synonymous	Exon 6 of 7	ENSP00000357823.3	Q9BYD2
	MRPL9	ENST00000368829.3	TSL:2	c.495T>G	p.Val165Val	synonymous	Exon 5 of 6	ENSP00000357822.3	Q5SZR1
	MRPL9	ENST00000467306.5	TSL:2	n.*268T>G		non_coding_transcript_exon	Exon 6 of 7	ENSP00000492374.1	A0A1W2PRK9

Frequencies

GnomAD3 genomes AF: 0.0000137 AC: 2 AN: 145784 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000262

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1381280 Hom.: 0 Cov.: 31 AF XY: 0.00000436 AC XY: 3 AN XY: 688234

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

African (AFR) AF: 0.0000342 AC: 1 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: 76380

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: 0.00 AC: 0 AN: 1077534

Other (OTH) AF: 0.0000529 AC: 3 AN: 56732

⚠️ 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: 0.0000137 AC: 2 AN: 145784 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 70900

African (AFR) AF: 0.0000262 AC: 1 AN: 38132

American (AMR) AF: 0.00 AC: 0 AN: 14276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5040

South Asian (SAS) AF: 0.00 AC: 0 AN: 4612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67298

Other (OTH) AF: 0.00 AC: 0 AN: 1972

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.1
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;