3-47501822-A-G

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2 PM5 PP3_Strong

The NM_001031703.3(ELP6):​c.353T>C​(p.Leu118Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,824 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. L118W) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ELP6 NM_001031703.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.19
• 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: Likely_pathogenic. The variant received 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: 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.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.973

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP6	NM_001031703.3	c.353T>C	p.Leu118Ser	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>C	p.Leu118Ser	missense_variant	Exon 5 of 7	1	NM_001031703.3	ENSP00000296149.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;T;T;T;T;T;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.80	T;.;T;T;T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.97	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.9	M;.;.;.;.;.;.;.
PhyloP100		8.2
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.4	D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.92
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;.;D;.;D;D
Polyphen		1.0	D;.;.;.;.;.;.;.
Vest4		0.84
MutPred		0.86		Gain of loop (P = 0.0166);.;.;.;.;.;.;.;
MVP		0.78
MPC		1.4
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.78
gMVP		0.80
Mutation Taster		=62/38	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: rs2108086458; hg19: chr3-47543312;