17-8379817-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000987.5(RPL26):​c.288C>T​(p.His96His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,080 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

RPL26
NM_000987.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.249
Variant links:
Genes affected
RPL26 (HGNC:10327): (ribosomal protein L26) 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 L24P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Mutations in this gene result in Diamond-Blackfan anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 17-8379817-G-A is Benign according to our data. Variant chr17-8379817-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1614534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.249 with no splicing effect.
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPL26NM_000987.5 linkc.288C>T p.His96His synonymous_variant Exon 3 of 4 ENST00000648839.1 NP_000978.1 P61254
RPL26NM_001315530.2 linkc.288C>T p.His96His synonymous_variant Exon 3 of 4 NP_001302459.1 P61254
RPL26NM_001315531.2 linkc.288C>T p.His96His synonymous_variant Exon 3 of 4 NP_001302460.1 P61254

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPL26ENST00000648839.1 linkc.288C>T p.His96His synonymous_variant Exon 3 of 4 NM_000987.5 ENSP00000498177.1 P61254
ENSG00000263809ENST00000582471.1 linkn.288C>T non_coding_transcript_exon_variant Exon 3 of 6 5 ENSP00000463847.1 J3QQQ9

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000320
AC:
8
AN:
250356
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135266
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000530
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000356
AC:
52
AN:
1460878
Hom.:
0
Cov.:
30
AF XY:
0.0000316
AC XY:
23
AN XY:
726698
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.00
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:
0.0000441
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000903
Hom.:
0
Bravo
AF:
0.0000416

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Diamond-Blackfan anemia Benign:2
Jun 09, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Oct 11, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
0.60
DANN
Benign
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs573206384; hg19: chr17-8283135; COSMIC: COSV53446804; COSMIC: COSV53446804; API