rs1057519974
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP2PP3_ModeratePP5
The NM_005648.4(ELOC):c.235T>A(p.Tyr79Asn) variant causes a missense 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 Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y79F) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 32)
Consequence
ELOC
NM_005648.4 missense
NM_005648.4 missense
Scores
6
7
5
Clinical Significance
Conservation
PhyloP100: 6.95
Genes affected
ELOC (HGNC:11617): (elongin C) This gene encodes the protein elongin C, which is a subunit of the transcription factor B (SIII) complex. The SIII complex is composed of elongins A/A2, B and C. It activates elongation by RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin A functions as the transcriptionally active component of the SIII complex, whereas elongins B and C are regulatory subunits. Elongin A2 is specifically expressed in the testis, and capable of forming a stable complex with elongins B and C. The von Hippel-Lindau tumor suppressor protein binds to elongins B and C, and thereby inhibits transcription elongation. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been identified. [provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr8-73946733-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376558.Status of the report is no_assertion_criteria_provided, 0 stars.
PP2
?
Missense variant where missense usually causes diseases, ELOC
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.866
PP5
?
Variant 8-73946734-A-T is Pathogenic according to our data. Variant chr8-73946734-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376557.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELOC | NM_005648.4 | c.235T>A | p.Tyr79Asn | missense_variant | 4/4 | ENST00000520242.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELOC | ENST00000520242.6 | c.235T>A | p.Tyr79Asn | missense_variant | 4/4 | 1 | NM_005648.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Papillary renal cell carcinoma type 1 Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T;T;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.;M;M;M;M;M;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;.
Polyphen
B;B;.;B;B;B;B;B;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0749);Gain of MoRF binding (P = 0.0749);.;Gain of MoRF binding (P = 0.0749);Gain of MoRF binding (P = 0.0749);Gain of MoRF binding (P = 0.0749);Gain of MoRF binding (P = 0.0749);Gain of MoRF binding (P = 0.0749);Gain of MoRF binding (P = 0.0749);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at