12-56042066-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001029.5(RPS26):c.-101C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,234,466 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 Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: RPS26 NM_001029.5 5_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.746

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High AC in GnomAd at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS26	NM_001029.5	c.-101C>T		5_prime_UTR_variant	1/4	ENST00000646449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS26	ENST00000646449.2	c.-101C>T		5_prime_UTR_variant	1/4		NM_001029.5	P1
RPS26	ENST00000356464.10	c.-101C>T		5_prime_UTR_variant	2/5	1		P1
RPS26	ENST00000552361.1	c.-35+2C>T		splice_donor_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000203 AC: 22 AN: 1082262 Hom.: 0 Cov.: 15 AF XY: 0.0000216 AC XY: 12 AN XY: 555132

Gnomad4 AFR exome AF: 0.000437

Gnomad4 AMR exome AF: 0.0000232

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000130

Gnomad4 OTH exome AF: 0.000147

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74348

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000128

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

research

Gharavi Laboratory, Columbia University

Sep 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.8
Dann	Benign	0.76
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

Publications

LitVar

Other links and lift over

dbSNP: rs868693078; hg19: chr12-56435850;