chr17-7252534-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000396628.7(ELP5):​c.-17C>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 0.00000434 in 1,613,840 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 (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ELP5
ENST00000396628.7 5_prime_UTR

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.727
Variant links:
Genes affected
ELP5 (HGNC:30617): (elongator acetyltransferase complex subunit 5) Predicted to contribute to tRNA binding activity. Predicted to be involved in positive regulation of cell migration and tRNA modification. Located in cytosol and nucleoplasm. Part of elongator holoenzyme complex. [provided by Alliance of Genome Resources, Apr 2022]
CTDNEP1 (HGNC:19085): (CTD nuclear envelope phosphatase 1) Enables protein serine/threonine phosphatase activity. Involved in several processes, including positive regulation of triglyceride biosynthetic process; protein dephosphorylation; and protein localization to nucleus. Located in endoplasmic reticulum membrane; lipid droplet; and nuclear membrane. Part of Nem1-Spo7 phosphatase complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09118998).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ELP5NM_203414.3 linkuse as main transcriptc.-17C>T 5_prime_UTR_variant 1/8 ENST00000396628.7 NP_981959.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ELP5ENST00000396628.7 linkuse as main transcriptc.-17C>T 5_prime_UTR_variant 1/81 NM_203414.3 ENSP00000379869 P2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
249082
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
134952
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000356
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461524
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727052
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152316
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000460
Hom.:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 18, 2022The c.32C>T (p.T11I) alteration is located in exon 1 (coding exon 1) of the ELP5 gene. This alteration results from a C to T substitution at nucleotide position 32, causing the threonine (T) at amino acid position 11 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
8.2
DANN
Benign
0.75
DEOGEN2
Benign
0.017
.;.;T;.;.;T;T;.;T;.
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.37
T;T;T;.;T;.;T;.;.;T
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.091
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
.;.;L;L;L;L;.;L;L;L
MutationTaster
Benign
1.0
N;N;N;N;N;N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.25
.;.;N;.;N;N;.;.;N;.
REVEL
Benign
0.051
Sift
Uncertain
0.025
.;.;D;.;D;D;.;.;D;.
Sift4G
Benign
0.23
T;T;T;T;T;T;T;T;T;T
Polyphen
0.047, 0.14, 0.13
.;.;B;B;B;B;.;B;B;B
Vest4
0.13, 0.13, 0.16, 0.084, 0.075, 0.088
MutPred
0.22
Loss of phosphorylation at T11 (P = 0.0087);Loss of phosphorylation at T11 (P = 0.0087);Loss of phosphorylation at T11 (P = 0.0087);Loss of phosphorylation at T11 (P = 0.0087);Loss of phosphorylation at T11 (P = 0.0087);Loss of phosphorylation at T11 (P = 0.0087);Loss of phosphorylation at T11 (P = 0.0087);Loss of phosphorylation at T11 (P = 0.0087);Loss of phosphorylation at T11 (P = 0.0087);Loss of phosphorylation at T11 (P = 0.0087);
MVP
0.26
MPC
0.18
ClinPred
0.068
T
GERP RS
1.6
Varity_R
0.049
gMVP
0.44

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: rs748316662; hg19: chr17-7155853; COSMIC: COSV100021189; COSMIC: COSV100021189; API