15-69455181-C-G

Variant names:

• chr15-69455181-C-G
• rs144572149
• NM_001003.3:c.159C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001003.3(RPLP1):​c.159C>G​(p.Asn53Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N53S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPLP1 NM_001003.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472
• Publications: 0 publications found

Genes affected

RPLP1 (HGNC:10372): (ribosomal protein lateral stalk subunit P1) 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 phosphoprotein that is a component of the 60S subunit. The protein, which is a functional equivalent of the E. coli L7/L12 ribosomal protein, belongs to the L12P family of ribosomal proteins. It plays an important role in the elongation step of protein synthesis. Unlike most ribosomal proteins, which are basic, the encoded protein is acidic. Its C-terminal end is nearly identical to the C-terminal ends of the ribosomal phosphoproteins P0 and P2. The P1 protein can interact with P0 and P2 to form a pentameric complex consisting of P1 and P2 dimers, and a P0 monomer. The protein is located in the cytoplasm. Two alternatively spliced transcript variants that encode different proteins have 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]

KIF23-AS1 (HGNC:27075): (KIF23 and PAQR5 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26475435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPLP1	NM_001003.3	c.159C>G	p.Asn53Lys	missense_variant	Exon 3 of 4	ENST00000260379.11	NP_000994.1
RPLP1	NM_213725.2	c.84C>G	p.Asn28Lys	missense_variant	Exon 2 of 3		NP_998890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPLP1	ENST00000260379.11	c.159C>G	p.Asn53Lys	missense_variant	Exon 3 of 4	1	NM_001003.3	ENSP00000346037.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000426 AC: 1 AN: 234552 AF XY: 0.00000788

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: 0.00000926

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.94e-7 AC: 1 AN: 1440018 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715394

African (AFR) AF: 0.00 AC: 0 AN: 32374

American (AMR) AF: 0.00 AC: 0 AN: 39830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39452

South Asian (SAS) AF: 0.00 AC: 0 AN: 82886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4476

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103578

Other (OTH) AF: 0.00 AC: 0 AN: 59332

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.5
DANN	Benign	0.92
DEOGEN2	Uncertain	0.46	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.12	N;.
PhyloP100		0.47
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.19
Sift	Benign	0.25	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.076	B;.
Vest4		0.50
MutPred		0.54		Gain of methylation at N53 (P = 0.021);.;
MVP		0.33
MPC		0.22
ClinPred		0.24	T
GERP RS		-5.5
Varity_R		0.62
gMVP		0.61
Mutation Taster		=68/32	polymorphism

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: rs144572149; hg19: chr15-69747520;