3-138460020-T-G

Variant names:

• chr3-138460020-T-G
• NM_031913.5:c.724T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031913.5(ESYT3):​c.724T>G​(p.Phe242Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ESYT3 NM_031913.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.28
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.905

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.724T>G	p.Phe242Val	missense	Exon 6 of 23	NP_114119.2	A0FGR9-1
	ESYT3	NM_001322831.2		c.724T>G	p.Phe242Val	missense	Exon 6 of 24	NP_001309760.1	A0FGR9-1
	ESYT3	NM_001322834.2		c.724T>G	p.Phe242Val	missense	Exon 6 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.724T>G	p.Phe242Val	missense	Exon 6 of 23	ENSP00000374218.4	A0FGR9-1
	ESYT3	ENST00000942989.1		c.724T>G	p.Phe242Val	missense	Exon 6 of 23	ENSP00000613048.1
	ESYT3	ENST00000942987.1		c.724T>G	p.Phe242Val	missense	Exon 6 of 23	ENSP00000613046.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Pathogenic	0.91
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.87
MutPred		0.66		Loss of catalytic residue at F242 (P = 0.0344)
MVP		0.89
MPC		0.73
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.91
gMVP		0.82
Mutation Taster		=9/91	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr3-138178862;