17-7252991-A-G

Variant names:

• chr17-7252991-A-G
• NM_203414.3:c.181A>G

Variant summary

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

The NM_203414.3(ELP5):​c.181A>G​(p.Asn61Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELP5 NM_203414.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79

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]

ENSG00000262302 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
ELP5	NM_203414.3	c.181A>G	p.Asn61Asp	missense_variant	Exon 3 of 8	ENST00000396628.7	NP_981959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP5	ENST00000396628.7	c.181A>G	p.Asn61Asp	missense_variant	Exon 3 of 8	1	NM_203414.3	ENSP00000379869.3
ENSG00000262302	ENST00000577138.1	n.224-5648T>C		intron_variant	Intron 1 of 3	3		ENSP00000460571.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.229A>G (p.N77D) alteration is located in exon 3 (coding exon 3) of the ELP5 gene. This alteration results from a A to G substitution at nucleotide position 229, causing the asparagine (N) at amino acid position 77 to be replaced by an aspartic acid (D). 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	0.27
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	.;.;T;.;.;T;T;.;T;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.76	T;T;T;.;T;.;T;.;.;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.5	.;.;M;M;M;M;.;M;M;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.1	.;.;N;.;D;N;.;.;N;.
REVEL	Benign	0.13
Sift	Benign	0.15	.;.;T;.;T;T;.;.;T;.
Sift4G	Pathogenic	0.0	D;D;T;D;D;T;D;D;T;D
Polyphen		0.94, 0.98, 0.93	.;.;P;D;P;P;.;P;P;D
Vest4		0.56, 0.56, 0.52
MutPred		0.69		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.59
MPC		0.66
ClinPred		0.96	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.22

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.

Other links and lift over

hg19: chr17-7156310;