Genetic Variant ELP5:p.Pro73Ser (chr17-7254611-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_203414.3(ELP5):c.217C>T(p.Pro73Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ELP5
NM_203414.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

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]

ELP5 links:

ENSG00000262302 (HGNC:):

ENSG00000262302 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.957

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP5	NM_203414.3 link	c.217C>T	p.Pro73Ser	missense_variant	Exon 4 of 8	ENST00000396628.7	NP_981959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP5	ENST00000396628.7 link	c.217C>T	p.Pro73Ser	missense_variant	Exon 4 of 8	1	NM_203414.3	ENSP00000379869.3		Q8TE02
ENSG00000262302	ENST00000577138.1 link	n.223+7210G>A		intron_variant	Intron 1 of 3	3		ENSP00000460571.1		I3L3M4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251234

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135802

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727130

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

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.265C>T (p.P89S) alteration is located in exon 4 (coding exon 4) of the ELP5 gene. This alteration results from a C to T substitution at nucleotide position 265, causing the proline (P) at amino acid position 89 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

.;.;T;.;.;T;T;.;T;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.86

D;D;D;.;D;.;D;.;.;D

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.96

D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.37

MutationAssessor

Uncertain

2.8

.;.;M;M;M;M;.;M;M;M

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.5

.;.;D;.;D;D;.;.;D;.

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

.;.;D;.;D;D;.;.;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D

Polyphen

1.0

.;.;D;D;D;D;.;D;D;D

Vest4

0.68, 0.65, 0.65, 0.65

MutPred

0.83

Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);

MVP

0.89

MPC

0.63

ClinPred

0.99

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.76

gMVP

0.72

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over