Genetic Variant RPL27:c.-20G>T (chr17-42998454-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_000988.5(RPL27):c.-20G>T variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPL27
NM_000988.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.939

Publications

4 publications found

Variant links:

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

RPL27 links:

LOC124904006 (HGNC:):

LOC124904006 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL27	NM_000988.5	MANE Select	c.-20G>T	5_prime_UTR	Exon 1 of 5	NP_000979.1	P61353
RPL27	NM_001349922.2		c.-297G>T	5_prime_UTR	Exon 1 of 4	NP_001336851.1	P61353
RPL27	NM_001349921.2		c.-3+39G>T	intron	N/A	NP_001336850.1	P61353

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL27	ENST00000253788.12	TSL:1 MANE Select	c.-20G>T	5_prime_UTR	Exon 1 of 5	ENSP00000253788.5	P61353
RPL27	ENST00000911442.1		c.-20G>T	5_prime_UTR	Exon 1 of 6	ENSP00000581501.1
RPL27	ENST00000905376.1		c.-81G>T	5_prime_UTR	Exon 1 of 5	ENSP00000575435.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

147236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

79950

African (AFR)

AF:

0.00

AC:

AN:

2926

American (AMR)

AF:

0.00

AC:

AN:

4028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4124

East Asian (EAS)

AF:

0.00

AC:

AN:

5942

South Asian (SAS)

AF:

0.00

AC:

AN:

24862

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

584

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

88498

Other (OTH)

AF:

0.00

AC:

AN:

8110

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000540

Hom.:

9039

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

-0.94

PromoterAI

-0.035

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.55

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.55

Position offset: -6

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over