rs201949984

Variant names:

• chr3-138460654-C-G
• rs201949984
• NM_031913.5:c.782C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-138460654-C-G
• chr3-138460654-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031913.5(ESYT3):​c.782C>G​(p.Ala261Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,720 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A261V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ESYT3 NM_031913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27779484).

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.782C>G	p.Ala261Gly	missense	Exon 7 of 23	NP_114119.2	A0FGR9-1
	ESYT3	NM_001322831.2		c.782C>G	p.Ala261Gly	missense	Exon 7 of 24	NP_001309760.1	A0FGR9-1
	ESYT3	NM_001322834.2		c.782C>G	p.Ala261Gly	missense	Exon 7 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.782C>G	p.Ala261Gly	missense	Exon 7 of 23	ENSP00000374218.4	A0FGR9-1
	ESYT3	ENST00000942989.1		c.773C>G	p.Ala258Gly	missense	Exon 7 of 23	ENSP00000613048.1
	ESYT3	ENST00000942987.1		c.782C>G	p.Ala261Gly	missense	Exon 7 of 23	ENSP00000613046.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461720 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727160

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.094
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.039
Sift	Benign	0.078	T
Sift4G	Uncertain	0.049	D
Polyphen		0.74	P
Vest4		0.54
MutPred		0.49		Loss of stability (P = 0.0336)
MVP		0.23
MPC		0.29
ClinPred		0.41	T
GERP RS		3.3
Varity_R		0.090
gMVP		0.58
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs201949984; hg19: chr3-138179496;