Genetic Variant RPS27:p.Lys22Lys (chr1-153991174-A-G) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001030.6(RPS27):c.66A>G(p.Lys22Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000819 in 1,599,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

RPS27
NM_001030.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.13

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 1-153991174-A-G is Benign according to our data. Variant chr1-153991174-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 745884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.13 with no splicing effect.

BS2

High AC in GnomAd4 at 27 AD,Unknown gene.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS27	NM_001030.6	MANE Select	c.66A>G	p.Lys22Lys	synonymous	Exon 2 of 4	NP_001021.1	P42677
RPS27	NM_001349946.2		c.-31A>G		5_prime_UTR	Exon 3 of 5	NP_001336875.1
RPS27	NM_001349947.2		c.-31A>G		5_prime_UTR	Exon 2 of 4	NP_001336876.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS27	ENST00000651669.1	MANE Select	c.66A>G	p.Lys22Lys	synonymous	Exon 2 of 4	ENSP00000499044.1	P42677
RPS27	ENST00000936804.1		c.187A>G	p.Thr63Ala	missense	Exon 3 of 5	ENSP00000606863.1
RPS27	ENST00000936806.1		c.189A>G	p.Lys63Lys	synonymous	Exon 3 of 5	ENSP00000606865.1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000731

AC:

AN:

232528

AF XY:

0.0000798

show subpopulations

Gnomad AFR exome

AF:

0.000138

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000138

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000718

AC:

104

AN:

1447616

Hom.:

Cov.:

AF XY:

0.0000737

AC XY:

AN XY:

718776

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33256

American (AMR)

AF:

0.00

AC:

AN:

43680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25704

East Asian (EAS)

AF:

0.00

AC:

AN:

39596

South Asian (SAS)

AF:

0.00

AC:

AN:

84702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5198

European-Non Finnish (NFE)

AF:

0.0000870

AC:

AN:

1103306

Other (OTH)

AF:

0.0000168

AC:

AN:

59694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000177

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.000314

AC:

AN:

41432

American (AMR)

AF:

0.0000655

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68038

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.0000772

Hom.:

Bravo

AF:

0.000162

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.1

PromoterAI

-0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over