Variant chr13-46777532-T-C 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_001984.2(ESD):c.692A>G(p.Asp231Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000444 in 1,611,640 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 4 hom. )

Consequence

ESD
NM_001984.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.01

Variant links:

Genes affected

ESD (HGNC:3465): (esterase D) This gene encodes a serine hydrolase that belongs to the esterase D family. The encoded enzyme is active toward numerous substrates including O-acetylated sialic acids, and it may be involved in the recycling of sialic acids. This gene is used as a genetic marker for retinoblastoma and Wilson's disease. [provided by RefSeq, Feb 2009]

ESD 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=0.008594215).

BP6

Variant 13-46777532-T-C is Benign according to our data. Variant chr13-46777532-T-C is described in ClinVar as [Benign]. Clinvar id is 732050.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ESD	NM_001984.2 linkuse as main transcript	c.692A>G	p.Asp231Gly	missense_variant	9/10	ENST00000378720.8
ESD	XM_005266278.4 linkuse as main transcript	c.692A>G	p.Asp231Gly	missense_variant	9/10
ESD	XM_011534954.2 linkuse as main transcript	c.692A>G	p.Asp231Gly	missense_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ESD	ENST00000378720.8 linkuse as main transcript	c.692A>G	p.Asp231Gly	missense_variant	9/10	1	NM_001984.2	P1
ESD	ENST00000471867.3 linkuse as main transcript	c.692A>G	p.Asp231Gly	missense_variant	9/9	2
ESD	ENST00000378697.5 linkuse as main transcript	c.605A>G	p.Asp202Gly	missense_variant	10/11	5
ESD	ENST00000412582.5 linkuse as main transcript	c.536A>G	p.Asp179Gly	missense_variant	5/6	3

Frequencies

GnomAD3 genomes

AF:

0.000671

AC:

102

AN:

151910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00154

AC:

385

AN:

250538

Hom.:

AF XY:

0.00134

AC XY:

182

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0202

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.000420

AC:

613

AN:

1459612

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

284

AN XY:

726054

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0137

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000929

GnomAD4 genome

AF:

0.000678

AC:

103

AN:

152028

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0161

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000772

Hom.:

Bravo

AF:

0.000839

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00125

AC:

152

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

D;D

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

0.86

D;D

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.094

Sift

Benign

0.070

T;T

Sift4G

Uncertain

0.039

D;D

Polyphen

0.0

B;.

Vest4

0.36

MVP

0.70

MPC

0.11

ClinPred

0.045

GERP RS

4.9

Varity_R

0.46

gMVP

0.50

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