3-138460020-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESYT3	NM_031913.5	c.724T>G	p.Phe242Val	missense_variant	Exon 6 of 23	ENST00000389567.9	NP_114119.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESYT3	ENST00000389567.9	c.724T>G	p.Phe242Val	missense_variant	Exon 6 of 23	1	NM_031913.5	ENSP00000374218.4
ESYT3	ENST00000289135.4	c.724T>G	p.Phe242Val	missense_variant	Exon 6 of 8	5		ENSP00000289135.4
ESYT3	ENST00000486831.5	n.937T>G		non_coding_transcript_exon_variant	Exon 6 of 22	5
ESYT3	ENST00000490835.5	n.724T>G		non_coding_transcript_exon_variant	Exon 6 of 18	2		ENSP00000417388.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.724T>G (p.F242V) alteration is located in exon 6 (coding exon 6) of the ESYT3 gene. This alteration results from a T to G substitution at nucleotide position 724, causing the phenylalanine (F) at amino acid position 242 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.7	D;D
REVEL	Pathogenic	0.91
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.99	D;.
Vest4		0.87
MutPred		0.66		Loss of catalytic residue at F242 (P = 0.0344);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-138178862;