8-28110384-A-C

Variant names:

• chr8-28110384-A-C
• NM_018091.6:c.408A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018091.6(ELP3):​c.408A>C​(p.Arg136Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 32)
• Consequence: ELP3 NM_018091.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

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.408A>C	p.Arg136Ser	missense	Exon 6 of 15	NP_060561.3
	ELP3	NM_001284222.2		c.366A>C	p.Arg122Ser	missense	Exon 6 of 15	NP_001271151.1	Q9H9T3-2
	ELP3	NM_001284220.2		c.192A>C	p.Arg64Ser	missense	Exon 5 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.408A>C	p.Arg136Ser	missense	Exon 6 of 15	ENSP00000256398.8	Q9H9T3-1
	ELP3	ENST00000521015.5	TSL:1	c.366A>C	p.Arg122Ser	missense	Exon 6 of 15	ENSP00000428449.1	Q9H9T3-2
	ELP3	ENST00000900018.1		c.408A>C	p.Arg136Ser	missense	Exon 6 of 16	ENSP00000570077.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	4.2	H
PhyloP100		2.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.97	D
Vest4		0.97
MutPred		0.72		Loss of MoRF binding (P = 0.0385)
MVP		0.60
MPC		1.3
ClinPred		1.0	D
GERP RS		2.3
Varity_R		0.89
gMVP		0.93
Mutation Taster		=1/99	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: chr8-27967901;