Variant 20-41362193-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000332312.4(EMILIN3):c.1376G>C(p.Gly459Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000911 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

EMILIN3
ENST00000332312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.103

Variant links:

Genes affected

EMILIN3 (HGNC:16123): (elastin microfibril interfacer 3) Enables identical protein binding activity. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

EMILIN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044858992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMILIN3	NM_052846.2 linkuse as main transcript	c.1376G>C	p.Gly459Ala	missense_variant	4/4	ENST00000332312.4	NP_443078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMILIN3	ENST00000332312.4 linkuse as main transcript	c.1376G>C	p.Gly459Ala	missense_variant	4/4	1	NM_052846.2	ENSP00000332806	P1	Q9NT22-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000220

AC:

AN:

249904

Hom.:

AF XY:

0.000237

AC XY:

AN XY:

135130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.000187

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.0000855

AC:

125

AN:

1461676

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000826

Gnomad4 NFE exome

AF:

0.0000558

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000145

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000202

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2022

The c.1376G>C (p.G459A) alteration is located in exon 4 (coding exon 4) of the EMILIN3 gene. This alteration results from a G to C substitution at nucleotide position 1376, causing the glycine (G) at amino acid position 459 to be replaced by an alanine (A). 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

0.077

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.2

DANN

Benign

0.70

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.54

M_CAP

Benign

0.0094

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.86

REVEL

Benign

0.060

Sift

Benign

0.73

Sift4G

Benign

0.25

Polyphen

0.52

Vest4

0.19

MutPred

0.71

Loss of stability (P = 0.0821);

MVP

0.17

MPC

0.22

ClinPred

0.016

GERP RS

0.12

Varity_R

0.042

gMVP

0.30

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over