17-42998811-C-G

Position:

• chr17-42998811-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000988.5(RPL27):​c.61C>G​(p.Arg21Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPL27 NM_000988.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.93

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL27	NM_000988.5	c.61C>G	p.Arg21Gly	missense_variant	2/5	ENST00000253788.12	NP_000979.1
LOC124904006	XR_007065759.1	n.789G>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL27	ENST00000253788.12	c.61C>G	p.Arg21Gly	missense_variant	2/5	1	NM_000988.5	ENSP00000253788	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.61C>G (p.R21G) alteration is located in exon 2 (coding exon 1) of the RPL27 gene. This alteration results from a C to G substitution at nucleotide position 61, causing the arginine (R) at amino acid position 21 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;D;D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	.;.;T
M_CAP	Uncertain	0.092	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.1	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.2	.;D;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.0030	.;D;.
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.94	P;P;P
Vest4		0.90
MutPred		0.56		Loss of MoRF binding (P = 0.0073);Loss of MoRF binding (P = 0.0073);Loss of MoRF binding (P = 0.0073);
MVP		0.46
MPC		0.43
ClinPred		1.0	D
GERP RS		3.6
Varity_R		0.87
gMVP		0.95

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: chr17-41150828;