Genetic Variant NM_001030.6:c.7-9C>A (chr1-153991106-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001030.6(RPS27):c.7-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 1,556,946 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

RPS27
NM_001030.6 intron

Scores

Splicing: ADA: 0.001204

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.481

Publications

0 publications found

Variant links:

Genes affected

RPS27 (HGNC:10416): (ribosomal protein S27) 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 S27e family of ribosomal proteins and component of the 40S subunit. The encoded protein contains a C4-type zinc finger domain that can bind to zinc and may bind to nucleic acid. Mutations in this gene have been identified in numerous melanoma patients and in at least one patient with Diamond-Blackfan anemia (DBA). Elevated expression of this gene has been observed in various human cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2018]

RPS27 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia 17
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

RPS27 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS27	NM_001030.6	MANE Select	c.7-9C>A	intron	N/A	NP_001021.1	P42677
RPS27	NM_001349946.2		c.-90-9C>A	intron	N/A	NP_001336875.1
RPS27	NM_001349947.2		c.-90-9C>A	intron	N/A	NP_001336876.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS27	ENST00000651669.1	MANE Select	c.7-9C>A	intron	N/A	ENSP00000499044.1	P42677
RPS27	ENST00000936806.1		c.130-9C>A	intron	N/A	ENSP00000606865.1
RPS27	ENST00000936804.1		c.128-9C>A	intron	N/A	ENSP00000606863.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.12e-7

AC:

AN:

1404796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31282

American (AMR)

AF:

0.00

AC:

AN:

36280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24246

East Asian (EAS)

AF:

0.00

AC:

AN:

38598

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4030

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079844

Other (OTH)

AF:

0.00

AC:

AN:

57744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.3

(source)

DANN

Benign

0.82

PhyloP100

0.48

PromoterAI

-0.0098

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0012

dbscSNV1_RF

Benign

0.13

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over