Genetic Variant ESYT3:p.Ala210Asp (chr3-138459234-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031913.5(ESYT3):c.629C>A(p.Ala210Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ESYT3
NM_031913.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Publications

0 publications found

Variant links:

Genes affected

ESYT3 (HGNC:24295): (extended synaptotagmin 3) Predicted to enable calcium ion binding activity and phospholipid binding activity. Predicted to be involved in endoplasmic reticulum-plasma membrane tethering and lipid transport. Located in endoplasmic reticulum-plasma membrane contact site. Is extrinsic component of cytoplasmic side of plasma membrane; integral component of plasma membrane; and intrinsic component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ESYT3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031913.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ESYT3	NM_031913.5	MANE Select	c.629C>A	p.Ala210Asp	missense	Exon 5 of 23	NP_114119.2	A0FGR9-1
ESYT3	NM_001322831.2		c.629C>A	p.Ala210Asp	missense	Exon 5 of 24	NP_001309760.1	A0FGR9-1
ESYT3	NM_001322834.2		c.629C>A	p.Ala210Asp	missense	Exon 5 of 23	NP_001309763.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ESYT3	ENST00000389567.9	TSL:1 MANE Select	c.629C>A	p.Ala210Asp	missense	Exon 5 of 23	ENSP00000374218.4	A0FGR9-1
ESYT3	ENST00000942989.1		c.629C>A	p.Ala210Asp	missense	Exon 5 of 23	ENSP00000613048.1
ESYT3	ENST00000942987.1		c.629C>A	p.Ala210Asp	missense	Exon 5 of 23	ENSP00000613046.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1407868

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698078

African (AFR)

AF:

0.00

AC:

AN:

32088

American (AMR)

AF:

0.00

AC:

AN:

42308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24644

East Asian (EAS)

AF:

0.00

AC:

AN:

37068

South Asian (SAS)

AF:

0.00

AC:

AN:

78504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5538

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078440

Other (OTH)

AF:

0.00

AC:

AN:

57476

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

0.15

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.099

MetaRNN

Uncertain

0.68

MetaSVM

Uncertain

-0.067

MutationAssessor

Uncertain

2.4

PhyloP100

1.8

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.57

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0080

Polyphen

0.66

Vest4

0.86

MutPred

0.48

Loss of catalytic residue at A210 (P = 0.0265)

MVP

0.64

MPC

0.68

ClinPred

0.98

GERP RS

4.1

Varity_R

0.79

gMVP

0.90

Mutation Taster

=71/29

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over