chr11-8684852-A-G

Variant names:

• chr11-8684852-A-G
• rs562282613
• NM_000990.5:c.278A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000990.5(RPL27A):​c.278A>G​(p.Asn93Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,614,158 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (1 hom.)
• Consequence: RPL27A NM_000990.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.98
• Publications: 0 publications found

Genes affected

RPL27A (HGNC:10329): (ribosomal protein L27a) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L15P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04985732).
• BS2: High AC in GnomAdExome4 at 23 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000990.5. 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
	RPL27A	NM_000990.5	MANE Select	c.278A>G	p.Asn93Ser	missense	Exon 4 of 5	NP_000981.1	P46776

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL27A	ENST00000314138.11	TSL:1 MANE Select	c.278A>G	p.Asn93Ser	missense	Exon 4 of 5	ENSP00000346015.5	P46776
	RPL27A	ENST00000530022.5	TSL:1	c.107A>G	p.Asn36Ser	missense	Exon 3 of 4	ENSP00000432671.1	E9PJD9
	RPL27A	ENST00000921544.1		c.278A>G	p.Asn93Ser	missense	Exon 4 of 5	ENSP00000591603.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251470 AF XY: 0.0000809

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461816 Hom.: 1 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111960

Other (OTH) AF: 0.0000994 AC: 6 AN: 60386

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74500

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.095
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.049
Sift	Benign	0.22	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.30		Gain of glycosylation at N93 (P = 0.0096)
MVP		0.53
MPC		0.73
ClinPred		0.14	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.061
gMVP		0.39
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs562282613; hg19: chr11-8706399;