Genetic Variant ELP6:p.Arg76Gln (chr3-47504426-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001031703.3(ELP6):c.227G>A(p.Arg76Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,607,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

ELP6
NM_001031703.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

Publications

1 publications found

Variant links:

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]

ELP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31446454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP6	NM_001031703.3 link	c.227G>A	p.Arg76Gln	missense_variant	Exon 4 of 7	ENST00000296149.9	NP_001026873.2	Q0PNE2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP6	ENST00000296149.9 link	c.227G>A	p.Arg76Gln	missense_variant	Exon 4 of 7	1	NM_001031703.3	ENSP00000296149.4		Q0PNE2-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000532

AC:

AN:

244138

AF XY:

0.0000528

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

276

AN:

1455172

Hom.:

Cov.:

AF XY:

0.000198

AC XY:

143

AN XY:

723608

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33252

American (AMR)

AF:

0.0000227

AC:

AN:

44064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26006

East Asian (EAS)

AF:

0.00

AC:

AN:

39304

South Asian (SAS)

AF:

0.00

AC:

AN:

85262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.000245

AC:

272

AN:

1108260

Other (OTH)

AF:

0.0000333

AC:

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68042

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000149

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000239

AC:

ExAC

AF:

0.0000496

AC:

EpiCase

AF:

0.000110

EpiControl

AF:

0.0000600

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 01, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.227G>A (p.R76Q) alteration is located in exon 4 (coding exon 4) of the ELP6 gene. This alteration results from a G to A substitution at nucleotide position 227, causing the arginine (R) at amino acid position 76 to be replaced by a glutamine (Q). 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

0.094

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.031

T;T;T;T;T;T;T;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.96

D;.;D;D;D;D;D;D

M_CAP

Benign

0.0081

MetaRNN

Benign

0.31

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.6

M;.;.;.;.;.;.;.

PhyloP100

2.6

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.9

N;N;N;N;N;N;N;D

REVEL

Benign

0.23

Sift

Benign

0.10

T;D;D;D;D;D;D;D

Sift4G

Benign

0.13

T;T;T;.;T;.;T;D

Polyphen

1.0

D;.;.;.;.;.;.;.

Vest4

0.47

MVP

0.68

MPC

1.1

ClinPred

0.36

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.089

gMVP

0.36

Mutation Taster

=83/17

polymorphism

(source)

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

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3-47504426-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over