3-47501822-A-C

Variant names:

• chr3-47501822-A-C
• rs2108086458
• NM_001031703.3:c.353T>G

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001031703.3(ELP6):​c.353T>G​(p.Leu118Trp) variant causes a missense change involving the alteration of a 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 Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ELP6 NM_001031703.3 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.19
• Publications: 1 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: Likely_pathogenic. The variant received 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979
• PP5: Variant 3-47501822-A-C is Pathogenic according to our data. Variant chr3-47501822-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1676202.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP6	NM_001031703.3	c.353T>G	p.Leu118Trp	missense_variant	Exon 5 of 7	ENST00000296149.9	NP_001026873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP6	ENST00000296149.9	c.353T>G	p.Leu118Trp	missense_variant	Exon 5 of 7	1	NM_001031703.3	ENSP00000296149.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Pathogenic:1

Mar 17, 2022

School of Medicine, Dokuz Eylül University

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Uncertain	0.45	T;T;T;T;T;T;T;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	T;.;T;T;T;T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.00050	T
MutationAssessor	Uncertain	2.9	M;.;.;.;.;.;.;.
PhyloP100		8.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.5	D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.89
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;.;D;.;D;D
Polyphen		1.0	D;.;.;.;.;.;.;.
Vest4		0.72
MutPred		0.89		Loss of stability (P = 0.0602);.;.;.;.;.;.;.;
MVP		0.78
MPC		1.5
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.74
gMVP		0.82
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2108086458; hg19: chr3-47543312;