rs148942765

Variant names:

• chr12-56043440-C-T
• rs148942765
• NM_001029.5:c.259C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-56043440-C-T
• chr12-56043440-C-A

Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_001029.5(RPS26):​c.259C>T​(p.Arg87*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPS26 NM_001029.5 stop_gained
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:4
• Conservation: PhyloP100: 4.61
• Publications: 3 publications found

Genes affected

RPS26 (HGNC:10414): (ribosomal protein S26) This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S26E family of ribosomal proteins. Mutations in this gene are found in Diamond-Blackfan anemia 10. There are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Aug 2017]

RPS26 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 10

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 18 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-56043440-C-T is Pathogenic according to our data. Variant chr12-56043440-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 187849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029.5. 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
	RPS26	NM_001029.5	MANE Select	c.259C>T	p.Arg87*	stop_gained	Exon 3 of 4	NP_001020.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS26	ENST00000646449.2	MANE Select	c.259C>T	p.Arg87*	stop_gained	Exon 3 of 4	ENSP00000496643.1	P62854
	RPS26	ENST00000356464.10	TSL:1	c.259C>T	p.Arg87*	stop_gained	Exon 4 of 5	ENSP00000348849.5	P62854
	RPS26	ENST00000552361.1	TSL:5	c.259C>T	p.Arg87*	stop_gained	Exon 4 of 5	ENSP00000450339.1	P62854

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
2	-	-	Diamond-Blackfan anemia 10 (2)
1	-	-	Diamond-Blackfan anemia (1)
1	-	-	Diamond-Blackfan anemia 15 with mandibulofacial dysostosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		4.6
Vest4		0.92
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=4/196	disease causing (ClinVar)

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: rs148942765; hg19: chr12-56437224;