3-138434865-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031913.5(ESYT3):​c.67C>T​(p.Pro23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,397,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. P23T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: ESYT3 NM_031913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05677882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESYT3	NM_031913.5	c.67C>T	p.Pro23Ser	missense_variant	Exon 1 of 23	ENST00000389567.9	NP_114119.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESYT3	ENST00000389567.9	c.67C>T	p.Pro23Ser	missense_variant	Exon 1 of 23	1	NM_031913.5	ENSP00000374218.4
ESYT3	ENST00000289135.4	c.67C>T	p.Pro23Ser	missense_variant	Exon 1 of 8	5		ENSP00000289135.4
ESYT3	ENST00000486831.5	n.280C>T		non_coding_transcript_exon_variant	Exon 1 of 22	5
ESYT3	ENST00000490835.5	n.67C>T		non_coding_transcript_exon_variant	Exon 1 of 18	2		ENSP00000417388.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000165 AC: 23 AN: 1397430 Hom.: 0 Cov.: 31 AF XY: 0.0000160 AC XY: 11 AN XY: 689198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000204

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.5
DANN	Benign	0.91
DEOGEN2	Benign	0.0039	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.016
Sift	Benign	0.55	T;T
Sift4G	Benign	0.81	T;T
Polyphen		0.020	B;.
Vest4		0.083
MutPred		0.17		Gain of phosphorylation at P23 (P = 0.0271);Gain of phosphorylation at P23 (P = 0.0271);
MVP		0.10
MPC		0.14
ClinPred		0.028	T
GERP RS		2.1
Varity_R		0.021
gMVP		0.70

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-138153707;