Variant 17-7252593-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000396628.7(ELP5):c.43C>G(p.Arg15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ELP5
ENST00000396628.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELP5	NM_203414.3 linkuse as main transcript	c.43C>G	p.Arg15Gly	missense_variant	1/8	ENST00000396628.7	NP_981959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP5	ENST00000396628.7 linkuse as main transcript	c.43C>G	p.Arg15Gly	missense_variant	1/8	1	NM_203414.3	ENSP00000379869	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460078

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726254

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2022

The c.91C>G (p.R31G) alteration is located in exon 1 (coding exon 1) of the ELP5 gene. This alteration results from a C to G substitution at nucleotide position 91, causing the arginine (R) at amino acid position 31 to be replaced by a glycine (G). 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

0.47

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

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

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.77

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

M_CAP

Benign

0.083

MetaRNN

Uncertain

0.51

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

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.6

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.2

.;.;N;.;D;N;.;.;N;.

REVEL

Benign

0.25

Sift

Uncertain

0.010

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

Sift4G

Uncertain

0.012

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

Polyphen

1.0

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

Vest4

0.59, 0.62, 0.59, 0.58, 0.63

MutPred

0.68

Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);

MVP

0.78

MPC

0.71

ClinPred

0.94

GERP RS

3.9

Varity_R

0.34

gMVP

0.49

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over