Variant 20-41361731-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_052846.2(EMILIN3):c.1838T>C(p.Leu613Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 1,613,380 control chromosomes in the GnomAD database, including 29 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 26 hom. )

Consequence

EMILIN3
NM_052846.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.553

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004256934).

BP6

Variant 20-41361731-A-G is Benign according to our data. Variant chr20-41361731-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2652331.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMILIN3	NM_052846.2 link	c.1838T>C	p.Leu613Ser	missense_variant	4/4	ENST00000332312.4	NP_443078.1	Q9NT22-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMILIN3	ENST00000332312.4 link	c.1838T>C	p.Leu613Ser	missense_variant	4/4	1	NM_052846.2	ENSP00000332806.3		Q9NT22-1

Frequencies

GnomAD3 genomes

AF:

0.00376

AC:

572

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00583

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00355

AC:

891

AN:

250864

Hom.:

AF XY:

0.00376

AC XY:

510

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.000741

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.000837

Gnomad NFE exome

AF:

0.00598

Gnomad OTH exome

AF:

0.00425

GnomAD4 exome

AF:

0.00431

AC:

6295

AN:

1461016

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

3138

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00226

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.00110

Gnomad4 NFE exome

AF:

0.00509

Gnomad4 OTH exome

AF:

0.00373

GnomAD4 genome

AF:

0.00375

AC:

571

AN:

152364

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

274

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00542

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00582

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00421

Hom.:

Bravo

AF:

0.00399

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00362

AC:

440

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00643

EpiControl

AF:

0.00628

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

EMILIN3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.6

DANN

Benign

0.75

DEOGEN2

Benign

0.011

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.40

M_CAP

Benign

0.064

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.0

REVEL

Benign

0.14

Sift

Benign

0.26

Sift4G

Benign

0.48

Polyphen

0.0080

Vest4

0.10

MVP

0.44

MPC

0.21

ClinPred

0.0039

GERP RS

0.32

Varity_R

0.045

gMVP

0.17

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