chr3-47504426-C-A

Variant names:

• chr3-47504426-C-A
• rs201253001
• NM_001031703.3:c.227G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001031703.3(ELP6):​c.227G>T​(p.Arg76Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R76Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ELP6 NM_001031703.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64
• Publications: 0 publications found

Genes affected

ELP6 (HGNC:25976): (elongator acetyltransferase complex subunit 6) Predicted to be involved in positive regulation of cell migration. Located in cytosol and nucleus. Part of elongator holoenzyme complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP6	NM_001031703.3	c.227G>T	p.Arg76Leu	missense_variant	Exon 4 of 7	ENST00000296149.9	NP_001026873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP6	ENST00000296149.9	c.227G>T	p.Arg76Leu	missense_variant	Exon 4 of 7	1	NM_001031703.3	ENSP00000296149.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455172 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723608

African (AFR) AF: 0.00 AC: 0 AN: 33252

American (AMR) AF: 0.00 AC: 0 AN: 44064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.00 AC: 0 AN: 39304

South Asian (SAS) AF: 0.00 AC: 0 AN: 85262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108260

Other (OTH) AF: 0.00 AC: 0 AN: 60108

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T;T;T;T;T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D;.;D;D;D;D;D;D
M_CAP	Benign	0.0078	T
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.6	M;.;.;.;.;.;.;.
PhyloP100		2.6
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.9	D;D;D;D;D;D;D;D
REVEL	Benign	0.25
Sift	Benign	0.12	T;D;D;D;D;D;D;D
Sift4G	Benign	0.14	T;T;T;.;T;.;T;D
Polyphen		0.99	D;.;.;.;.;.;.;.
Vest4		0.54
MutPred		0.74		Loss of methylation at R76 (P = 0.0335);.;.;.;.;.;.;.;
MVP		0.76
MPC		1.1
ClinPred		0.97	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.57
Mutation Taster		=57/43	polymorphism

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

dbSNP: rs201253001; hg19: chr3-47545916;