8-28137831-A-C

Variant names:

• chr8-28137831-A-C
• NM_018091.6:c.1040A>C

Variant summary

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

The NM_018091.6(ELP3):​c.1040A>C​(p.Glu347Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ELP3 NM_018091.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.16

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 rank	MANE	Protein	UniProt
ELP3	NM_018091.6	c.1040A>C	p.Glu347Ala	missense_variant	Exon 10 of 15	ENST00000256398.13	NP_060561.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP3	ENST00000256398.13	c.1040A>C	p.Glu347Ala	missense_variant	Exon 10 of 15	1	NM_018091.6	ENSP00000256398.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461768 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1040A>C (p.E347A) alteration is located in exon 10 (coding exon 10) of the ELP3 gene. This alteration results from a A to C substitution at nucleotide position 1040, causing the glutamic acid (E) at amino acid position 347 to be replaced by an alanine (A). 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	0.16
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	.;T;.;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.44	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	.;M;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-4.1	D;D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0060	D;D;D;D;D
Sift4G	Uncertain	0.032	D;D;D;D;D
Polyphen		0.0010	.;B;.;.;.
Vest4		0.55
MutPred		0.39		.;Gain of MoRF binding (P = 0.0789);.;.;.;
MVP		0.57
MPC		0.49
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.27
gMVP		0.88

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: chr8-27995348;