Genetic Variant ELP5:p.Leu6Ser (chr17-7252567-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_203414.3(ELP5):c.17T>C(p.Leu6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ELP5
NM_203414.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.409

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:

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]

CTDNEP1 links:

Genome browser will be placed here

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=0.15626696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP5	NM_203414.3 link	c.17T>C	p.Leu6Ser	missense_variant	Exon 1 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.17T>C	p.Leu6Ser	missense_variant	Exon 1 of 8	1	NM_203414.3	ENSP00000379869.3		Q8TE02
ENSG00000262302	ENST00000577138.1 link	n.224-5224A>G		intron_variant	Intron 1 of 3	3		ENSP00000460571.1		I3L3M4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248434

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134670

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:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461258

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726938

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.65T>C (p.L22S) alteration is located in exon 1 (coding exon 1) of the ELP5 gene. This alteration results from a T to C substitution at nucleotide position 65, causing the leucine (L) at amino acid position 22 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

Benign

0.17

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.14

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

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.49

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

M_CAP

Benign

0.014

MetaRNN

Benign

0.16

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.5

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

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.1

.;.;N;.;N;N;.;.;N;.

REVEL

Benign

0.10

Sift

Benign

0.20

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

Sift4G

Uncertain

0.028

D;D;T;D;D;T;D;D;T;D

Polyphen

0.053, 0.077

.;.;B;B;B;B;.;B;B;B

Vest4

0.20, 0.21, 0.25, 0.25, 0.18, 0.22

MutPred

0.71

Gain of disorder (P = 0.0099);Gain of disorder (P = 0.0099);Gain of disorder (P = 0.0099);Gain of disorder (P = 0.0099);Gain of disorder (P = 0.0099);Gain of disorder (P = 0.0099);Gain of disorder (P = 0.0099);Gain of disorder (P = 0.0099);Gain of disorder (P = 0.0099);Gain of disorder (P = 0.0099);

MVP

0.47

MPC

0.21

ClinPred

0.047

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.073

gMVP

0.23

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