chr17-42998504-C-A

Variant names:

• chr17-42998504-C-A
• rs691997
• ENST00000589913.6:c.-247C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001349922.2(RPL27):​c.-247C>A 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_001349922.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 3 publications found

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

LOC124904006 (HGNC:):

ACMG classification

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=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349922.2. 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
	RPL27	NM_000988.5	MANE Select	c.-3+33C>A		intron	N/A	NP_000979.1	P61353
	RPL27	NM_001349922.2		c.-247C>A		5_prime_UTR	Exon 1 of 4	NP_001336851.1	P61353
	RPL27	NM_001349921.2		c.-3+89C>A		intron	N/A	NP_001336850.1	P61353

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL27	ENST00000589913.6	TSL:1	c.-247C>A		5_prime_UTR	Exon 1 of 4	ENSP00000464813.1	P61353
	RPL27	ENST00000253788.12	TSL:1 MANE Select	c.-3+33C>A		intron	N/A	ENSP00000253788.5	P61353
	RPL27	ENST00000905376.1		c.-31C>A		5_prime_UTR	Exon 1 of 5	ENSP00000575435.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 250444 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 133928

African (AFR) AF: 0.00 AC: 0 AN: 5544

American (AMR) AF: 0.00 AC: 0 AN: 6968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7946

East Asian (EAS) AF: 0.00 AC: 0 AN: 14260

South Asian (SAS) AF: 0.00 AC: 0 AN: 31174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1130

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 152878

Other (OTH) AF: 0.00 AC: 0 AN: 14470

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.78
PhyloP100		-0.31
PromoterAI		-0.060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs691997; hg19: chr17-41150521;