4-39456250-T-TG

Variant names:

• chr4-39456250-T-TG
• rs3216720
• NM_000661.5:c.391+155_391+156insC

Variant summary

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

The NM_000661.5(RPL9):​c.391+155_391+156insC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33931 hom., cov: 0)
  • Exomes 𝑓: 0.69 (157301 hom.)
• Consequence: RPL9 NM_000661.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.87
• Publications: 5 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-39456250-T-TG is Benign according to our data. Variant chr4-39456250-T-TG is described in ClinVar as Benign. ClinVar VariationId is 1268644.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL9	NM_000661.5	c.391+155_391+156insC		intron_variant	Intron 5 of 7	ENST00000295955.14	NP_000652.2
RPL9	NM_001024921.4	c.391+155_391+156insC		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.391+155_391+156insC		intron_variant	Intron 5 of 7	1	NM_000661.5	ENSP00000346022.7

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100877 AN: 151978 Hom.: 33901 Cov.: 0

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.835

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.686

GnomAD2 exomes AF: 0.713 AC: 104167 AN: 146046 AF XY: 0.715

Gnomad AFR exome AF: 0.533

Gnomad AMR exome AF: 0.793

Gnomad ASJ exome AF: 0.694

Gnomad EAS exome AF: 0.737

Gnomad FIN exome AF: 0.649

Gnomad NFE exome AF: 0.696

Gnomad OTH exome AF: 0.721

GnomAD4 exome AF: 0.694 AC: 449319 AN: 647172 Hom.: 157301 Cov.: 9 AF XY: 0.698 AC XY: 239873 AN XY: 343790

African (AFR) AF: 0.537 AC: 8997 AN: 16760

American (AMR) AF: 0.788 AC: 26184 AN: 33218

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 13706 AN: 19580

East Asian (EAS) AF: 0.728 AC: 23136 AN: 31770

South Asian (SAS) AF: 0.764 AC: 47556 AN: 62280

European-Finnish (FIN) AF: 0.650 AC: 30415 AN: 46816

Middle Eastern (MID) AF: 0.634 AC: 2633 AN: 4156

European-Non Finnish (NFE) AF: 0.686 AC: 274269 AN: 399660

Other (OTH) AF: 0.681 AC: 22423 AN: 32932

GnomAD4 genome AF: 0.664 AC: 100963 AN: 152096 Hom.: 33931 Cov.: 0 AF XY: 0.664 AC XY: 49388 AN XY: 74336

African (AFR) AF: 0.550 AC: 22810 AN: 41456

American (AMR) AF: 0.762 AC: 11654 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2460 AN: 3466

East Asian (EAS) AF: 0.736 AC: 3821 AN: 5190

South Asian (SAS) AF: 0.772 AC: 3727 AN: 4826

European-Finnish (FIN) AF: 0.645 AC: 6807 AN: 10556

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47269 AN: 68004

Other (OTH) AF: 0.691 AC: 1456 AN: 2108

Alfa AF: 0.624 Hom.: 3781

Bravo AF: 0.668

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.9
Mutation Taster		=21/79	disease causing

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: rs3216720; hg19: chr4-39457870; COSMIC: COSV107219359; COSMIC: COSV107219359;