chr3-138435109-A-T

Variant names:

• chr3-138435109-A-T
• rs769401642
• NM_031913.5:c.311A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_031913.5(ESYT3):​c.311A>T​(p.Gln104Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000489 in 1,432,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: ESYT3 NM_031913.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.31
• 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=0.08804256).
• BP6: Variant 3-138435109-A-T is Benign according to our data. Variant chr3-138435109-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3090685.Status of the report is criteria_provided_single_submitter, 1 stars.

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.311A>T	p.Gln104Leu	missense	Exon 1 of 23	NP_114119.2	A0FGR9-1
	ESYT3	NM_001322831.2		c.311A>T	p.Gln104Leu	missense	Exon 1 of 24	NP_001309760.1	A0FGR9-1
	ESYT3	NM_001322834.2		c.311A>T	p.Gln104Leu	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.311A>T	p.Gln104Leu	missense	Exon 1 of 23	ENSP00000374218.4	A0FGR9-1
	ESYT3	ENST00000942989.1		c.311A>T	p.Gln104Leu	missense	Exon 1 of 23	ENSP00000613048.1
	ESYT3	ENST00000942987.1		c.311A>T	p.Gln104Leu	missense	Exon 1 of 23	ENSP00000613046.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000242 AC: 5 AN: 206320 AF XY: 0.00000888

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000187

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000489 AC: 7 AN: 1432494 Hom.: 0 Cov.: 31 AF XY: 0.00000564 AC XY: 4 AN XY: 709158

African (AFR) AF: 0.00 AC: 0 AN: 33238

American (AMR) AF: 0.00 AC: 0 AN: 41652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25304

East Asian (EAS) AF: 0.0000513 AC: 2 AN: 38964

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00000364 AC: 4 AN: 1099380

Other (OTH) AF: 0.00 AC: 0 AN: 59408

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000252 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.16
Sift	Benign	0.34	T
Sift4G	Benign	0.17	T
Polyphen		0.47	P
Vest4		0.19
MutPred		0.45		Gain of catalytic residue at Q104 (P = 0.0126)
MVP		0.43
MPC		0.14
ClinPred		0.047	T
GERP RS		0.35
PromoterAI		0.066	Neutral
Varity_R		0.073
gMVP		0.52
Mutation Taster		=75/25	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: rs769401642; hg19: chr3-138153951;