rs2030508494

Variant names:

• chr3-138434865-C-A
• rs2030508494
• NM_031913.5:c.67C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-138434865-C-A
• chr3-138434865-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031913.5(ESYT3):​c.67C>A​(p.Pro23Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,549,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ESYT3 NM_031913.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.140
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059282064).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESYT3	NM_031913.5	MANE Select	c.67C>A	p.Pro23Thr	missense	Exon 1 of 23	NP_114119.2	A0FGR9-1
	ESYT3	NM_001322831.2		c.67C>A	p.Pro23Thr	missense	Exon 1 of 24	NP_001309760.1	A0FGR9-1
	ESYT3	NM_001322834.2		c.67C>A	p.Pro23Thr	missense	Exon 1 of 23	NP_001309763.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESYT3	ENST00000389567.9	TSL:1 MANE Select	c.67C>A	p.Pro23Thr	missense	Exon 1 of 23	ENSP00000374218.4	A0FGR9-1
	ESYT3	ENST00000942989.1		c.67C>A	p.Pro23Thr	missense	Exon 1 of 23	ENSP00000613048.1
	ESYT3	ENST00000942987.1		c.67C>A	p.Pro23Thr	missense	Exon 1 of 23	ENSP00000613046.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152104 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1397430 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 689198

African (AFR) AF: 0.00 AC: 0 AN: 31532

American (AMR) AF: 0.00 AC: 0 AN: 35744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25150

East Asian (EAS) AF: 0.0000559 AC: 2 AN: 35774

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078876

Other (OTH) AF: 0.00 AC: 0 AN: 57830

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152104 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.8
DANN	Benign	0.80
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.14
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.028
Sift	Benign	0.51	T
Sift4G	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.18		Loss of glycosylation at T20 (P = 0.0632)
MVP		0.10
MPC		0.16
ClinPred		0.060	T
GERP RS		2.1
PromoterAI		-0.017	Neutral
Varity_R		0.029
gMVP		0.69
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs2030508494; hg19: chr3-138153707;