8-28132391-T-G

Position:

• chr8-28132391-T-G

Variant summary

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

The NM_018091.6(ELP3):​c.893T>G​(p.Ile298Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELP3 NM_018091.6 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 4.13

Genes affected

ELP3 (HGNC:20696): (elongator acetyltransferase complex subunit 3) Enables acetyltransferase activity and phosphorylase kinase regulator activity. Involved in regulation of transcription by RNA polymerase II and tRNA wobble uridine modification. Located in cytosol and nucleolus. Part of elongator holoenzyme complex. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	Protein	UniProt
ELP3	NM_018091.6	c.893T>G	p.Ile298Ser	missense_variant	9/15	ENST00000256398.13	NP_060561.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP3	ENST00000256398.13	c.893T>G	p.Ile298Ser	missense_variant	9/15	1	NM_018091.6	ENSP00000256398.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

-

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	.;D;.;.;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.58	D;D;D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.0	.;M;.;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.3	D;D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		0.064	.;B;.;.;.
Vest4		0.62
MutPred		0.53		.;Gain of disorder (P = 0.0019);.;.;.;
MVP		0.79
MPC		0.94
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.61
gMVP		0.94

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: rs764954376; hg19: chr8-27989908;