3-47501762-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001031703.3(ELP6):​c.413A>G​(p.Tyr138Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 143,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Consequence

ELP6
NM_001031703.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0310

Publications

0 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08233383).
BP6
Variant 3-47501762-T-C is Benign according to our data. Variant chr3-47501762-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2300798.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ELP6NM_001031703.3 linkc.413A>G p.Tyr138Cys missense_variant Exon 5 of 7 ENST00000296149.9 NP_001026873.2 Q0PNE2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ELP6ENST00000296149.9 linkc.413A>G p.Tyr138Cys missense_variant Exon 5 of 7 1 NM_001031703.3 ENSP00000296149.4 Q0PNE2-1

Frequencies

GnomAD3 genomes
AF:
0.0000139
AC:
2
AN:
143952
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000517
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.0000139
AC:
2
AN:
143952
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
70428
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000517
AC:
2
AN:
38698
American (AMR)
AF:
0.00
AC:
0
AN:
14520
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3298
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4768
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4426
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10312
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
278
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
64836
Other (OTH)
AF:
0.00
AC:
0
AN:
1952
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.0000354
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jul 12, 2022
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.056
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
2.5
DANN
Benign
0.85
DEOGEN2
Benign
0.0078
T;T;T;T;T;T;T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.083
N
LIST_S2
Benign
0.71
T;.;T;T;T;T;T;T
M_CAP
Benign
0.00088
T
MetaRNN
Benign
0.082
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-1.5
N;.;.;.;.;.;.;.
PhyloP100
-0.031
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.30
N;N;N;N;N;N;N;N
REVEL
Benign
0.053
Sift
Benign
0.18
T;T;T;T;T;T;T;T
Sift4G
Benign
0.18
T;T;T;.;T;.;T;T
Polyphen
0.0
B;.;.;.;.;.;.;.
Vest4
0.094
MutPred
0.53
Loss of sheet (P = 0.1158);.;.;.;.;.;.;.;
MVP
0.28
MPC
0.45
ClinPred
0.029
T
GERP RS
-4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.040
gMVP
0.37
Mutation Taster
=95/5
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

Publications

Other links and lift over

dbSNP: rs1387178847; hg19: chr3-47543252; COSMIC: COSV106418417; COSMIC: COSV106418417; API