4-39454956-G-A

Variant names:

• chr4-39454956-G-A
• rs778833788
• NM_000661.5:c.392-12C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000661.5(RPL9):​c.392-12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,860 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RPL9 NM_000661.5 intron
• Scores: Splicing: ADA: 0.00008360
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.203
• Publications: 0 publications found

Genes affected

RPL9 (HGNC:10369): (ribosomal protein L9) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L6P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 4-39454956-G-A is Benign according to our data. Variant chr4-39454956-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2997655.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL9	NM_000661.5	c.392-12C>T		intron_variant	Intron 5 of 7	ENST00000295955.14	NP_000652.2
RPL9	NM_001024921.4	c.392-12C>T		intron_variant	Intron 5 of 7		NP_001020092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL9	ENST00000295955.14	c.392-12C>T		intron_variant	Intron 5 of 7	1	NM_000661.5	ENSP00000346022.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456860 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724898

African (AFR) AF: 0.00 AC: 0 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 44238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108690

Other (OTH) AF: 0.00 AC: 0 AN: 60258

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 28, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.6
DANN	Benign	0.68
PhyloP100		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000084
dbscSNV1_RF	Benign	0.022
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: rs778833788; hg19: chr4-39456576;