17-7252940-G-T

Position:

• chr17-7252940-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_203414.3(ELP5):​c.130G>T​(p.Gly44Cys) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELP5 NM_203414.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.80

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELP5	NM_203414.3	c.130G>T	p.Gly44Cys	missense_variant	3/8	ENST00000396628.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP5	ENST00000396628.7	c.130G>T	p.Gly44Cys	missense_variant	3/8	1	NM_203414.3	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2023

The c.178G>T (p.G60C) alteration is located in exon 3 (coding exon 3) of the ELP5 gene. This alteration results from a G to T substitution at nucleotide position 178, causing the glycine (G) at amino acid position 60 to be replaced by a cysteine (C). 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	0.26
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Benign	0.042
Eigen_PC	Benign	0.055
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.82	T;T;T;.;T;.;T;.;.;T
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.68	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.61	T
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D
Polyphen		0.21, 1.0, 0.35	.;.;B;D;B;B;.;B;B;D
Vest4		0.81, 0.80, 0.80
MutPred		0.81		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP		0.77
MPC		0.65
ClinPred		0.98	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.60

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

Other links and lift over

dbSNP: rs1312951663; hg19: chr17-7156259;