NM_001022.4:c.173-3357C>T

Variant names:

• chr19-41865674-C-T
• rs7259596
• NM_001022.4:c.173-3357C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001022.4(RPS19):​c.173-3357C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,780 control chromosomes in the GnomAD database, including 15,105 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (15105 hom., cov: 30)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 4 publications found

Genes affected

RPS19 (HGNC:10402): (ribosomal protein S19) 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 40S subunit. The protein belongs to the S19E family of ribosomal proteins. It is located in the cytoplasm. Mutations in this gene cause Diamond-Blackfan anemia (DBA), a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors, in a subset of patients. This suggests a possible extra-ribosomal function for this gene in erythropoietic differentiation and proliferation, in addition to its ribosomal function. Higher expression levels of this gene in some primary colon carcinomas compared to matched normal colon tissues has been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS19 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Diamond-Blackfan anemia 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001022.4. 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
	RPS19	NM_001022.4	MANE Select	c.173-3357C>T		intron	N/A	NP_001013.1	B0ZBD0
	RPS19	NM_001321485.2		c.186-3357C>T		intron	N/A	NP_001308414.1
	RPS19	NM_001321483.2		c.173-3357C>T		intron	N/A	NP_001308412.1	B0ZBD0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS19	ENST00000598742.6	TSL:1 MANE Select	c.173-3357C>T		intron	N/A	ENSP00000470972.1	P39019
	RPS19	ENST00000593863.5	TSL:3	c.173-3357C>T		intron	N/A	ENSP00000470004.1	P39019
	RPS19	ENST00000600467.6	TSL:2	c.173-3357C>T		intron	N/A	ENSP00000469228.2	P39019

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62914 AN: 151660 Hom.: 15109 Cov.: 30

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.474

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.415 AC: 62913 AN: 151780 Hom.: 15105 Cov.: 30 AF XY: 0.420 AC XY: 31139 AN XY: 74182

African (AFR) AF: 0.154 AC: 6364 AN: 41450

American (AMR) AF: 0.489 AC: 7447 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2129 AN: 3464

East Asian (EAS) AF: 0.458 AC: 2357 AN: 5144

South Asian (SAS) AF: 0.571 AC: 2743 AN: 4806

European-Finnish (FIN) AF: 0.515 AC: 5427 AN: 10542

Middle Eastern (MID) AF: 0.671 AC: 192 AN: 286

European-Non Finnish (NFE) AF: 0.512 AC: 34759 AN: 67858

Other (OTH) AF: 0.469 AC: 986 AN: 2102

Alfa AF: 0.439 Hom.: 2059

Bravo AF: 0.398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
PhyloP100		-2.5

Splicing

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

Other links and lift over

dbSNP: rs7259596; hg19: chr19-42369743;