19-55391659-C-A

Variant names:

• chr19-55391659-C-A
• NM_000991.5:c.*3327C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136135.2(RPL28):​c.430C>A​(p.Arg144Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RPL28 NM_001136135.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

Genes affected

RPL28 (HGNC:10330): (ribosomal protein L28) 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 L28E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. 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 encoding distinct isoforms.[provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07843426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL28	NM_000991.5	c.*3327C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000344063.7	NP_000982.2
RPL28	NM_001136135.2	c.430C>A	p.Arg144Ser	missense_variant	Exon 5 of 5		NP_001129607.1
RPL28	NM_001136134.1	c.*3443C>A		3_prime_UTR_variant	Exon 4 of 4		NP_001129606.1
RPL28	NM_001363697.1	c.324+3611C>A		intron_variant	Intron 4 of 4		NP_001350626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL28	ENST00000344063.7	c.*3327C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_000991.5	ENSP00000342787.3
RPL28	ENST00000426763.3	n.5179C>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
RPL28	ENST00000558815.5	c.430C>A	p.Arg144Ser	missense_variant	Exon 5 of 5	2		ENSP00000452909.1
RPL28	ENST00000560055.5	c.324+3611C>A		intron_variant	Intron 4 of 4	3		ENSP00000452763.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390850 Hom.: 0 Cov.: 28 AF XY: 0.00000146 AC XY: 1 AN XY: 686228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.33
DANN	Benign	0.80
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.22	N
Sift	Pathogenic	0.0	D
Vest4		0.20
MVP		0.28
MPC		0.66
ClinPred		0.22	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55903027;