Genetic Variant NM_133181.4:c.1167A>G (chr1-109753150-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_133181.4(EPS8L3):c.1167A>G(p.Ser389Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,612,672 control chromosomes in the GnomAD database, including 326,142 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 37610 hom., cov: 31)

Exomes 𝑓: 0.62 ( 288532 hom. )

Consequence

EPS8L3
NM_133181.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09

Variant links:

Genes affected

EPS8L3 (HGNC:21297): (EPS8 signaling adaptor L3) This gene encodes a protein that is related to epidermal growth factor receptor pathway substrate 8 (EPS8), a substrate for the epidermal growth factor receptor. The function of this protein is unknown. Alternatively spliced transcript variants encoding different isoforms exist. [provided by RefSeq, Jul 2008]

EPS8L3 links:

GSTM5 (HGNC:4637): (glutathione S-transferase mu 5) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. [provided by RefSeq, Jul 2008]

GSTM5 links:

ENSG00000241720 (HGNC:):

ENSG00000241720 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP7

Synonymous conserved (PhyloP=-2.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS8L3	NM_133181.4 link	c.1167A>G	p.Ser389Ser	synonymous_variant	Exon 13 of 19	ENST00000361965.9	NP_573444.2	Q8TE67-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS8L3	ENST00000361965.9 link	c.1167A>G	p.Ser389Ser	synonymous_variant	Exon 13 of 19	1	NM_133181.4	ENSP00000355255.4		Q8TE67-1

Frequencies

GnomAD3 genomes

AF:

0.692

AC:

105021

AN:

151856

Hom.:

37553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.876

Gnomad AMI

AF:

0.652

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.838

Gnomad SAS

AF:

0.723

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.644

GnomAD3 exomes

AF:

0.655

AC:

164052

AN:

250510

Hom.:

54976

AF XY:

0.649

AC XY:

87892

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.880

Gnomad AMR exome

AF:

0.670

Gnomad ASJ exome

AF:

0.569

Gnomad EAS exome

AF:

0.841

Gnomad SAS exome

AF:

0.720

Gnomad FIN exome

AF:

0.564

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.600

GnomAD4 exome

AF:

0.625

AC:

912883

AN:

1460698

Hom.:

288532

Cov.:

AF XY:

0.626

AC XY:

455078

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.883

Gnomad4 AMR exome

AF:

0.668

Gnomad4 ASJ exome

AF:

0.572

Gnomad4 EAS exome

AF:

0.827

Gnomad4 SAS exome

AF:

0.715

Gnomad4 FIN exome

AF:

0.564

Gnomad4 NFE exome

AF:

0.605

Gnomad4 OTH exome

AF:

0.637

GnomAD4 genome

AF:

0.692

AC:

105138

AN:

151974

Hom.:

37610

Cov.:

AF XY:

0.690

AC XY:

51211

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.876

Gnomad4 AMR

AF:

0.642

Gnomad4 ASJ

AF:

0.573

Gnomad4 EAS

AF:

0.837

Gnomad4 SAS

AF:

0.723

Gnomad4 FIN

AF:

0.572

Gnomad4 NFE

AF:

0.605

Gnomad4 OTH

AF:

0.647

Alfa

AF:

0.618

Hom.:

42920

Bravo

AF:

0.703

Asia WGS

AF:

0.755

AC:

2627

AN:

3478

EpiCase

AF:

0.591

EpiControl

AF:

0.583

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.20

DANN

Benign

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over