17-43000006-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

RPL27 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 16

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

LOC124904006 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000988.5. 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
	RPL27	NM_000988.5	MANE Select	c.155A>T	p.Lys52Ile	missense	Exon 3 of 5	NP_000979.1	P61353
	RPL27	NM_001349921.2		c.155A>T	p.Lys52Ile	missense	Exon 3 of 5	NP_001336850.1	P61353
	RPL27	NM_001349922.2		c.155A>T	p.Lys52Ile	missense	Exon 2 of 4	NP_001336851.1	P61353

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL27	ENST00000253788.12	TSL:1 MANE Select	c.155A>T	p.Lys52Ile	missense	Exon 3 of 5	ENSP00000253788.5	P61353
	RPL27	ENST00000589913.6	TSL:1	c.155A>T	p.Lys52Ile	missense	Exon 2 of 4	ENSP00000464813.1	P61353
	RPL27	ENST00000911442.1		c.245A>T	p.Lys82Ile	missense	Exon 4 of 6	ENSP00000581501.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		9.3
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.0070	B
Vest4		0.72
MutPred		0.65		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
Mutation Taster		=200/100	polymorphism

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

Other links and lift over

dbSNP: rs1422169310; hg19: chr17-41152023;