chr17-42998807-C-T

Variant names:

• chr17-42998807-C-T
• NM_000988.5:c.57C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000988.5(RPL27):​c.57C>T​(p.Ser19Ser) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPL27 NM_000988.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.660
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 17-42998807-C-T is Benign according to our data. Variant chr17-42998807-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3674222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.66 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL27	NM_000988.5	MANE Select	c.57C>T	p.Ser19Ser	synonymous	Exon 2 of 5	NP_000979.1	P61353
	RPL27	NM_001349921.2		c.57C>T	p.Ser19Ser	synonymous	Exon 2 of 5	NP_001336850.1	P61353
	RPL27	NM_001349922.2		c.57C>T	p.Ser19Ser	synonymous	Exon 1 of 4	NP_001336851.1	P61353

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL27	ENST00000253788.12	TSL:1 MANE Select	c.57C>T	p.Ser19Ser	synonymous	Exon 2 of 5	ENSP00000253788.5	P61353
	RPL27	ENST00000589913.6	TSL:1	c.57C>T	p.Ser19Ser	synonymous	Exon 1 of 4	ENSP00000464813.1	P61353
	RPL27	ENST00000911442.1		c.57C>T	p.Ser19Ser	synonymous	Exon 2 of 6	ENSP00000581501.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.7
DANN	Benign	0.91
PhyloP100		-0.66
PromoterAI		-0.066	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7

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

hg19: chr17-41150824;