NM_001031703.3:c.578A>G

Variant names:

• chr3-47498380-T-C
• rs149565751
• NM_001031703.3:c.578A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001031703.3(ELP6):​c.578A>G​(p.Asn193Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000761 in 1,613,704 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N193D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00078 (0 hom.)
• Consequence: ELP6 NM_001031703.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.767
• Publications: 2 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_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01112017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP6	NM_001031703.3	c.578A>G	p.Asn193Ser	missense_variant	Exon 6 of 7	ENST00000296149.9	NP_001026873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP6	ENST00000296149.9	c.578A>G	p.Asn193Ser	missense_variant	Exon 6 of 7	1	NM_001031703.3	ENSP00000296149.4

Frequencies

GnomAD3 genomes AF: 0.000578 AC: 88 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000983

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000586 AC: 146 AN: 249082 AF XY: 0.000547

Gnomad AFR exome AF: 0.0000645

Gnomad AMR exome AF: 0.000637

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000474

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000780 AC: 1140 AN: 1461408 Hom.: 0 Cov.: 62 AF XY: 0.000744 AC XY: 541 AN XY: 727020

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000783 AC: 35 AN: 44722

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

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

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.0000944 AC: 5 AN: 52948

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.000937 AC: 1042 AN: 1112006

Other (OTH) AF: 0.000596 AC: 36 AN: 60392

GnomAD4 genome AF: 0.000578 AC: 88 AN: 152296 Hom.: 0 Cov.: 33 AF XY: 0.000430 AC XY: 32 AN XY: 74474

African (AFR) AF: 0.0000722 AC: 3 AN: 41572

American (AMR) AF: 0.000982 AC: 15 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000985 AC: 67 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000964 Hom.: 0

Bravo AF: 0.000672

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00106 AC: 9

ExAC AF: 0.000586 AC: 71

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.000948

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.578A>G (p.N193S) alteration is located in exon 6 (coding exon 6) of the ELP6 gene. This alteration results from a A to G substitution at nucleotide position 578, causing the asparagine (N) at amino acid position 193 to be replaced by a serine (S). 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	0.091
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.4
DANN	Benign	0.93
DEOGEN2	Benign	0.011	T;T;T;T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.69	T;.;T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.011	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.83	L;.;.;.;.
PhyloP100		0.77
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.017
Sift	Benign	0.48	T;T;T;T;T
Sift4G	Benign	0.53	T;T;T;.;T
Polyphen		0.019	B;.;.;.;.
Vest4		0.21
MVP		0.32
MPC		0.31
ClinPred		0.0051	T
GERP RS		2.1
Varity_R		0.031
gMVP		0.11
Mutation Taster		=92/8	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: rs149565751; hg19: chr3-47539870;