chr8-28137740-C-T

Variant names:

• chr8-28137740-C-T
• NM_018091.6:c.949C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018091.6(ELP3):​c.949C>T​(p.Leu317Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELP3 NM_018091.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.04
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018091.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP3	NM_018091.6	MANE Select	c.949C>T	p.Leu317Phe	missense	Exon 10 of 15	NP_060561.3
	ELP3	NM_001284222.2		c.907C>T	p.Leu303Phe	missense	Exon 10 of 15	NP_001271151.1	Q9H9T3-2
	ELP3	NM_001284220.2		c.733C>T	p.Leu245Phe	missense	Exon 9 of 14	NP_001271149.1	B4DKA4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP3	ENST00000256398.13	TSL:1 MANE Select	c.949C>T	p.Leu317Phe	missense	Exon 10 of 15	ENSP00000256398.8	Q9H9T3-1
	ELP3	ENST00000521015.5	TSL:1	c.907C>T	p.Leu303Phe	missense	Exon 10 of 15	ENSP00000428449.1	Q9H9T3-2
	ELP3	ENST00000900018.1		c.949C>T	p.Leu317Phe	missense	Exon 10 of 16	ENSP00000570077.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.23
Sift	Benign	0.064	T
Sift4G	Pathogenic	0.0010	D
Polyphen		0.13	B
Vest4		0.90
MutPred		0.63		Gain of methylation at K316 (P = 0.0256)
MVP		0.54
MPC		0.57
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.43
gMVP		0.94
Mutation Taster		=27/73	disease causing

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

Other links and lift over

hg19: chr8-27995257;