NM_000988.5:c.155A>T

Variant names:

• chr17-43000006-A-T
• rs1422169310
• NM_000988.5:c.155A>T

Variant summary

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

The NM_000988.5(RPL27):​c.155A>T​(p.Lys52Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K52R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL27 NM_000988.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.28

Genes affected

RPL27 (HGNC:10328): (ribosomal protein L27) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L27e family of ribosomal proteins and a component of the 60S subunit. A splice site mutation in this gene has been identified in a Diamond-Blackfan anemia (DBA) patient. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Mar 2017]

LOC124904006 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL27	NM_000988.5	c.155A>T	p.Lys52Ile	missense_variant	Exon 3 of 5	ENST00000253788.12	NP_000979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL27	ENST00000253788.12	c.155A>T	p.Lys52Ile	missense_variant	Exon 3 of 5	1	NM_000988.5	ENSP00000253788.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D;D;D
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	.;.;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	3.3	M;M;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.7	.;D;.
REVEL	Uncertain	0.44
Sift	Uncertain	0.0030	.;D;.
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.0070	B;B;B
Vest4		0.72
MutPred		0.65		Loss of methylation at K52 (P = 0.0138);Loss of methylation at K52 (P = 0.0138);Loss of methylation at K52 (P = 0.0138);
MVP		0.53
MPC		1.5
ClinPred		0.99	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1422169310; hg19: chr17-41152023;