rs61762299

Variant names:

• chr19-41871323-AC-A
• rs61762299
• NM_001022.4:c.412-27delC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001022.4(RPS19):​c.412-27delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,460,820 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: RPS19 NM_001022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414
• Publications: 1 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: ClinGen, Orphanet
• Diamond-Blackfan anemia 1

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

ACMG classification

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

• BS2: High AC in GnomAdExome4 at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS19	NM_001022.4	c.412-27delC		intron_variant	Intron 5 of 5	ENST00000598742.6	NP_001013.1
RPS19	NM_001321485.2	c.425-27delC		intron_variant	Intron 5 of 5		NP_001308414.1
RPS19	NM_001321483.2	c.412-27delC		intron_variant	Intron 5 of 5		NP_001308412.1
RPS19	NM_001321484.2	c.412-27delC		intron_variant	Intron 5 of 5		NP_001308413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS19	ENST00000598742.6	c.412-27delC		intron_variant	Intron 5 of 5	1	NM_001022.4	ENSP00000470972.1
RPS19	ENST00000593863.5	c.412-27delC		intron_variant	Intron 5 of 5	3		ENSP00000470004.1
RPS19	ENST00000600467.6	c.412-27delC		intron_variant	Intron 5 of 5	2		ENSP00000469228.2
RPS19	ENST00000221975.6	c.190-27delC		intron_variant	Intron 5 of 5	3		ENSP00000221975.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251432 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000459 AC: 67 AN: 1460820 Hom.: 0 Cov.: 30 AF XY: 0.0000427 AC XY: 31 AN XY: 726822

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111046

Other (OTH) AF: 0.000166 AC: 10 AN: 60368

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.41
La Branchor		0.71
BranchPoint Hunter		3.0

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: rs61762299; hg19: chr19-42375391;